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As I write this editorial, it is almost 14 months since I first developed hypertension medications https://www.kraenzle.com/cost-of-lasix-at-walmart/ symptoms and my journey with long hypertension medications buy lasix tablets continues. In their guideline on long hypertension medications NICE/SIGN define post-hypertension medications syndrome as signs and symptoms that develop during or after a hypertension medications , continuing for more than 12 weeks, and not explained by an alternative diagnosis buy lasix tablets. More information about long hypertension medications can be found in the blog written by @jakesuett and me in September 2020.

Data from the Office for National Statistics in April 2021 estimated that 1.1âmillion people in the UK reported experiencing some form of long hypertension medications buy lasix tablets symptoms. Despite this, the UK Government continues to focus on the outcomes of hypertension medications being binary. Dying or buy lasix tablets surviving.

Box 1 provides details about some useful sources of information on long hypertension medications.Box 1 Useful sources of information about long hypertension medicationsNICE/SIGN rapid guideline published in December 2020.The NIHR review of evidence. Living with hypertension medicationsâsecond Review (March 2021).Paper in nature in April 2021 provides a summary of how post acute hypertension medications (long hypertension medications) can affect different organ systems.Paper published in March 2021 describing the range of signs and symptoms experienced by people with long hypertension medications via a social media survey.Everyoneâs long hypertension medications journey buy lasix tablets is different. Recovery is not linear with many relapses along the way.

Fourteen months on, I am better than I was but buy lasix tablets still not fit enough to return to work and need to be careful not to do too much. My ongoing symptoms include:Breathlessnessâe.g. After having a shower or walking short distances.Brain fogâunable to read for more than 15â20 min or concentrate on anything for buy lasix tablets more than 30 min.Headache.Fatigue.Poor temperature control and hot flushes.Deterioration in my eyesightâpotentially due to steroids.Tingling in faceSwollen glands.Nausea.I am one of the lucky onesâI was reviewed at a (virtual) long hypertension medications clinic in February 2021.

As suggested by the NICE/SIGN guidelines, I had some tests ordered to rule out any organic causes for my symptoms. The blood tests buy lasix tablets showed that I had developed type 2 diabetes. A brain MRI indicated I have had a stroke at some point.Nowadays, there is an expectation that most illnesses can be cured.

This makes it more buy lasix tablets difficult when there are no answers. As a buy lasix tablets patient group we struggled, and in many cases, are still struggling, to get access to the tests we needed which exacerbated this situation. This is perhaps not surprising in the middle of a lasix.

I always buy lasix tablets felt slightly uncomfortable fighting for access to tests when I knew the NHS was at crisis point but as a registered nurse had some knowledge as to where to turn for help. This was particularly helpful when I was rung with the results of my tests following my long hypertension medications clinic appointment. Having been told I buy lasix tablets had developed type 2 diabetes, the advice was to âgo on a low sugar dietâ and have my bloods tested again in a few months.

However, I was able to reach out to friends for advice as well as referring myself to the diabetes nurse at my GP practice. I am now on a low carb diet and have been prescribed metformin that would not have buy lasix tablets happened if I had just followed the initial advice. Getting advice about my stroke has not been so easy.

Over 6âweeks down the line, I am still awaiting my referral to the stroke clinic.On an intellectual level, as someone who has spent much of their nursing career promoting evidence-based practice, buy lasix tablets it has been interesting having a new disease and observing as information about potential treatments emerge. People within the long hypertension medications community were willing to try almost anything in an attempt to get better. A scene from the recent TV series Itâs a sin struck a chordâsomeone who thought they had AIDS/HIV in the mid 1980s ringing a hotline and asking whether a list of potential cures, including drinking bleach, would cure him.As a registered nurse and editor of Evidence Based Nursing, I found it challenging buy lasix tablets when other people with long hypertension medications appeared to me to be âgrasping at strawsâ and trying any treatment that was available despite a lack of evidence to support it.

I understand this is a reaction to the lack of available treatments as well as many people being told by the medical profession their symptoms were âall in their headâ. But, on occasion, it made it buy lasix tablets difficult being part of these groups. Going forward, we need robust research to identify treatments for long hypertension medications.

An international multistakeholder forum has recently produced buy lasix tablets a list of research priorities for long hypertension medications. Governments are beginning to allocate money for research into long hypertension medicationsâfor example, in the USA, the NIH has put US$1.15âbillion aside. These are definitely steps in the right direction but more needs to be done worldwide to care for those of us with Long hypertension medications.Ethics statementsPatient consent for publicationNot required.Using interpretative phenomenological analysis to explore multiperspectivesInterpretative phenomenological analysis (IPA) was originally developed in 1995 by Johnathan Smith as a method to undertake experiential research in psychology and has gained prominence across health and social sciences as a way to understand and buy lasix tablets interpret topics that are complex and emotionally laden, such as chronic illness experiences.1 2 IPA aims to uncover what a lived experience means to the individual through a process of in-depth reflective inquiry.3 The IPA draws on phenomenological thinking, with the purpose to return âto the things themselvesâ3 (p168).

However, IPA also acknowledges that we are each influenced by the worlds in which we live and the experiences buy lasix tablets we encounter. Therefore, IPA is an interpretative process between the researcher and researched, influenced predominantly by Heideggerâs interpretive phenomenology, hermeneutics and idiography. Within IPA, it is typical for researchers to select a buy lasix tablets small homogenous sample to explore the shared perspectives on a single phenomenon of interest4.

Within IPA studies, the focus has been on individual people living within diverse settings and populations such as chronic or long-term illnesses. The focus is on understandings of rich, lived experiences, and, given the small samples, IPA studies have typically not focused on those connected to the person living with diversity or buy lasix tablets disease. Recently, there has been an interest within IPA to suggest the value of capturing more complex data through multiple perspectives using designs and processes to address this shortcoming in IPA.4 This may involve the use of multiple participants and a range of data collection methods such as the use of dyads or focus groups.

The aim of this paper is to explore the utility of IPA approaches using multiperspectives through focusing on a specific case study to illustrate this approach.Case studyThis case study focuses on an IPA study that focused on the lived experiences of adolescents and young adults (AYA) buy lasix tablets and their family/significant other living with malignant melanoma (MM). Families and other people important to the experience can provide a logical and insightful perspectives on a shared psychosocial phenomenon. Multiperspective designs are buy lasix tablets gaining increasing prominence among researchers who recognise that an experience such as living with a long-term disease âis not solely located within the accounts of those with the diagnosisâ4 (p182).

For the purposes of this case study, the family/significant others were seen as integral to the experience for the AYA living with MM and their journey together in supporting one another through this experience.During the 1970s, melanoma in AYA was rare, but over the intervening decades, there has been a marked increase in the reported incidence of MM in AYA around the globe.5â7 There is a significant amount of biomedical empirical research evidence on melanoma but a dearth of qualitative research around the lived experience for AYA and their family/significant other living with this disease.A purposive sample of young participants, 16â26 years, were identified by the Clinical Nurse Specialists that ensured the participants were experiencing the same phenomenon.8â10 Although the intention was to carry out individual interviews with all the participants following the typical IPA approach, most of the AYA lived at home and the young participants expressed the desire for a shared interview, which was accommodated by the first author. The four individuals (n=4) and three-dyad interviews (n=6) allowed for the shared experience and the phenomena to be captured and understood through data analysis and interpretation.4 Although buy lasix tablets the use of individual and joint interviews had implications for data collection and analysisâsuch as the parent wishing to have their voice heard over their childâthe researcher had to ensure that questions were also directed to the young participant in order to capture both voices. In depth, semistructured interviews were undertaken within the AYAs primary treatment centre on the day of the outpatient appointment and they were often accompanied with someone who was significant in their journey.

Interviews lasted between 90 and 120 buy lasix tablets min.This study was novel to the experiences of AYA and family/significant other living with MM, which offers a new perspective on the dynamics that are present within the MM experience. Our findings can be valuable for both an AYA, family/significant other and health and social care professionals. Both AYA and the family/significant other seemed to consider the emotional implications of buy lasix tablets talking about the disease.

Throughout this process, participants seemed to strive for a shared understanding of the MM experience, a story buy lasix tablets that unified rather than divided them.Strengths and challengesA social phenomenological perspective demands an emphasis on understanding the participantâs experience of the world from their situation and then interpreting how that understanding is intersubjectively constructed.4 11 In-depth semistructured interviews, therefore, offered an appropriate and compelling method to generate data that permitted such insights and reflections, allowing participants to reconstruct their understandings of a phenomenon3 through narrative. Qualitative researchers are increasingly using âoint interviewsâ (dyad) to explore the lived experiences in health and capture the multiperspective. However, the decision of whether to interview participants separately or together as a dyad is an important consideration buy lasix tablets because it influences the nature of the data collected and having two different types of data.

Each transcript was analysed separately both for the AYA and then the family/significant other, whether as an individual or dyad. This was important as the researcher (first author) was not sure whether the findings for the AYA would be different buy lasix tablets from that of the family/significant other. There also needs to be time built into the study for the data analysis and IPA founders suggest following the IPA methodology, researchers should follow the key steps.3 Analysing the data individually allowed the narrative to âopen upâ and reveal the experiences of the participantâs as various âindividual partsâ and then as a âwholeâ.2 3 Throughout the data analysis, the six key steps supported the rigour, transparency and coherence of the findings.Findings of the case studyThis study was organised hierarchically into themes and following the iterative process of analysis, the 'Life interrupted' meta-narrative was identified from all the participantâs lives.

ÂLife interruptedâ speaks to the various ways buy lasix tablets that participantsâ lives were interrupted due to the cancer diagnosis, and the journey this disease took them on as well as the unsettling emotions that were experienced during this journey. This is woven into the whole journey experience and figure 1 illustrates the core conceptual thread and the interconnection between AYA and the family/significant other. The interconnection between the four super-ordinate and the 12 subthemes buy lasix tablets is also shown.

The ebb and flow of familial relationships can, in some situations, magnify the impact of the physical disease, with the emotional turmoil often rivalling the physical manifestation of the disease.8 11 Conversely, relationships may help the AYA and the family/significant other cope with the disease in a more positive and supportive way. The importance of these unique and changing relationships buy lasix tablets in living with MM should not be underestimated, and psychosocial research about YPs experiences of cancer would be enhanced through the further use and development of the multiperspective approach underpinned by IPA as used in this study, which is able to capture these dynamic inter-relationships. A visual representation is provided within figure 1 and how the individual voices were captured through the individual and dyad interview.Visual multi-perspective IPA design.

IPA, interpretative phenomenological analysis." data-icon-position data-hide-link-title="0">Figure 1 Visual multi-perspective buy lasix tablets IPA design. IPA, interpretative phenomenological analysis.ConclusionsThis paper presents experiences of life events and processes that are intersubjective and relational. Meaning is buy lasix tablets âin betweenâ us but is rarely studied that way in phenomenological inquiry.4 The meanings of events and processes are often contested and can sometimes be understood in a more complex manner when viewed from the multiple perspectives involved in the system that constitutes them.

Multiple perspective designs can be a useful way for IPA researchers to address research questions that engage with these phenomena.Ethics statementsPatient consent for publicationNot required..

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ÂListen to the podcast associated browse around this website with this article, which can also be found at ESC CardioTalk https://www.escardio.org/The-ESC/Whatwe-do/news/ESC-Cardio-Talk This editorial refers to âTime-to-treatment initiation of colchicine and cardiovascular outcomes lasix 200mg after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)ââ , by N. Bouabdallaoui et al., on page 4092. Virchowâs prophecyThe lasix 200mg late Rudolf L.C. Virchow (1821â1902) made a visionary statement when he wrote in one of his textbooks âAtherosclerosis is a chronic inflammation induced by cholesterolâ.1 It did not have much impact for several decades until the Russian scientist Nikolay Nikolaevich Anichkov (1885â1964) showed in his seminal experiments in the rabbit aorta that a high fat diet induces cholesterol-rich plaques.2 Thereafter, research focused on cholesterol rather than inflammation, with crucial epidemiological studies in Framingham and worldwide confirming an association of plasma lipid levels with the complications of atherosclerosis, i.e. Myocardial infarction, stroke, and sudden and premature death.3 The final proof of the cholesterol hypothesis came with the 4S trial using simvastatin in patients with coronary artery disease, demonstrating an impressive reduction of major cardiovascular events with pharmacological cholesterol lasix 200mg lowering.4 Rediscovering inflammationHowever, there was a remaining cardiovascular risk, and this led to the rediscovery of the true meaning of Virchowâs seminal statement.

First of all, it appeared from experimental studies that oxidized or otherwise modified cholesterol rather than native LDL-cholesterol (LDL-C)5,6 was involved and that dysfunctional HDL-C lost its protective function.7,8 The expression of adhesion molecules and, in turn, the presence of white blood cells such as monocytes, macrophages, and T cells in atherosclerotic plaques9 and the occluding thrombus in acute coronary syndromes (ACS)10 further corroborated the concept that inflammation might play a role. In 1994, the group of Attilio Maseris showed that acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) lasix 200mg predicted future cardiovascular events in patients with unstable angina.11 This observation was soon extended by Charles Hennekens and Paul Ridker to healthy individuals.12 In individuals at high cardiovascular risk with elevated CRP, but normal or midly elevated cholesterol, rosuvastatin lowered not only CRP, but also major cardiovascular events (MACE).13 Indeed, a mild anti-inflammatory action of statins had previously been demonstrated in small experimental trials. Thus, Virchowâs vision was indeed prophetic. However, how can this information be used clinically to the benefit of patients?. Inflammation and acute coronary syndromesA patient population lasix 200mg in which inflammation is particularly important are those with ACS.

Indeed, at the time of such an acute event, CRP and SAA plasma levels are several magnitudes higher than in patients with chronic coronary syndromes.10 Thus, it seems that ACS are associated with an inflammatory burst. Of note, inflammation is particularly high at the site of acute coronary occlusion, with an array of cytokines expressed, among them interleukins10 acting on lasix 200mg Toll-like receptors on white blood cells in a vicious cycle leading to an acute inflammatory storm.14 In this context, inflammation is a major trigger of plaque vulnerability, erosion, or rupture, and eventually coronary occlusion. After reperfusion, as occurs after successful primary percutaneous coronary intervention, inflammation importantly contributes to reperfusion injury also in the myocardium15 and in turn increases infarct size and scar formation, leading to left ventricular remodelling16 and MACE. Anti-inflammatory therapy as a new strategyBased on these data lasix 200mg and insights into the molecular mechanisms of ACS, inflammation became the new therapeutic frontier. After a few smaller proof-of-concept studies, the CANTOS trial using the interleukin-1Î² (IL-Î²) antagonist canakinumab proved the causal association of inflammation with MACE after ACS.17 Indeed, after 4 years, canakinumab reduced MACE (i.e.

Non-fatal myocardial infarction or stroke and cardiovascular death) overall by â¼15% 17 and by 26% in those with lasix 200mg an on-treatment CRP level <2 mg/L.18 Interestingly, canakinumab also reduced the occurrence of cancer, and in particular lung cancer, in these patients.19 The latter finding led the sponsor Novartis to decide to develop canakinumab for this indication rather than in cardiac patients.Thus, at this point, the clinical implementation of anti-inflammation came to a halt until recently when the results of the COLCOT trial were published. In this trial, patients who had survived an ACS were randomized within 30 days after the event to either placebo or colchicine at a low dose of 0.5 mg daily and were followed-up for a median of 2 years.20 Impressively, colchicine led to a 23% reduction of the primary endpoint of death, rescucitated cardiac arrest, ACS, stroke, and urgent hospitalization for angina requiring revascularization (however with the latter beiing the primary driver of the effect). Given the early inflammatory burst at the time of ACS, it remained unclearâas has been the case in CANTOSâwhether very early anti-inflammation might be even more advantageous or possibly rather dangerous. This question has now been addressed in the manuscript by Bouabdallaoui et al lasix 200mg. In the current issue of the European Heart Journal.21 They grouped the patients enrolled in COLCOT into three groups that had received investigational drugs (i.e.

Colchicine or placebo) within the first 3, 4â7, or 8 or more lasix 200mg days. Importantly, after a mean follow-up of 23 months, there was an amazing significant reduction of 48% in the primary endpoint in those receiving colchicine within 3 days or less, but only of 4â18% in those receiving the drug at a later timepoint. Thus, anti-inflammatory therapy seems to work best the sooner lasix 200mg it is provided after ACS. Given the fact that inflammation is most pronounced in the very early phase of an acute myocardial infarction, these results make a lot of sense. Learning from goutWhat might be the mechanism of action of colchicine lasix 200mg which traditionally is used in the management of gout?.

The mechanisms of action of colchicine are obviously multiple and not completely understood.22 First of all, colchicine binds to free tubulin, an Î±Î² heterodimer initially identified as the cellular colchicine-binding protein that forms microtubules upon polymerization and interacts with many regulatory cellular proteins (Figure 1). Thereby colchicine inhibits cell migration and cytokine release, particularly by white blood cells. Colchicine also modulates superoxide production by leucocytes23 which is in part responsible for the inhibition of neutrophil adhesion, extravasation, and recruitment by altering neutrophil L-selectin expression and endothelial cell E-selectin distribution, and suppressing the release of the chemotactic leukotriene B4 lasix 200mg. Whether all of these effects are secondary to the impact of colchicine on microtubules remains to be determined. Importantly, however, colchicine inhibits the Nod-Like Receptor Protein 3 (NLRP3) inflammasome lasix 200mg (while urate crystals activate i)t,24 thereby suppressing caspase-1 activation and the subsequent release of IL-1Î² and IL-18.

Figure 1). As the NLRP3 inflammasome is expressed in the myeloid lineage,25 colchicine lasix 200mg appears to mainly interfere with neutrophils and monocytes and macrophages, i.e. The innate immune system that is involved in ACS, rather than the adaptive immune system. Figure lasix 200mg 1Molecular effects of colchicine in white blood cells via tubulin and microtubuli as well as Nod-Like Receptor Protein 3 (NLRP3) inflammasome. Inset left, urate crystals.

Inset right, cholesterol crystals (modified from Imazio M, Gaita F. Heart April 2016 Vol 102 No 8).Figure 1Molecular effects of lasix 200mg colchicine in white blood cells via tubulin and microtubuli as well as Nod-Like Receptor Protein 3 (NLRP3) inflammasome. Inset left, urate crystals. Inset right, cholesterol crystals (modified lasix 200mg from Imazio M, Gaita F. Heart April 2016 Vol 102 No 8).

Colchicine after acute coronary syndromes? lasix 200mg. Should we now use colchicine in the very early phase of ACS as a remedy to reduce MACE?. First of all, colchicine is lasix 200mg cheap and, particularly at the low dose used in COLCOT, relatively well tolerated. Indeed, in the COLCOT trial, gastrointestinal side effects such as nausea and flatulence were quite rare, with 2.4% vs. 1.2% with placebo.

Obviously, as any anti-inflammatory drug, colchicine lasix 200mg increases the risk of . Pneumonia was rare, but indeed more common, with 0.9% vs. 0.4% with lasix 200mg colchicine and placebo, respectively. Should we therefore avoid prescribing colchicine for the elderly who are at risk of pneumonia or provide them with pneumococcal vaccination?. Indeed, acute s may precipitate myocardial infarction, while influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in this risk, but may actually be protective.26 As such, this may be a reasonable precaution in this context.A second question is whether colchicine would be suitable for all ACS lasix 200mg patients or only for those with signs of excessive inflammation?.

Indeed, not all patients with ACS have signs of inflammation. Typically, out-of-the-blue infarctions are triggered by other stimuli (such as shear stress, pulsatility, spasm, etc.), while in heralded infarction inflammation plays a primary role.10,27 Unfortunatly, CRP or SAA were not assessed in COLCOT and hence a more personalized use of this drug awaits further studies. Overall, however, the main COLCOT trial and now this important subanalysis open the door for an even more effective treatment of patients with ACS with remaining inflammatory risk.Conflict lasix 200mg of interest. There are no conflicts of interest for this Editorial. However, the author has received grants lasix 200mg for his ACS research from Amgen, AstraZeneca, Eli Lilly, Medtronic, and Sanofi, and honoraria for consulting and lecturing from Amgen and Sanofi.The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

References1Virchow R. Die Cellularpathologie in ihrer BegrÃ¼ndung auf physiologische und lasix 200mg pathologische Gewebelehre A. Berlin. Hirschwald. 1858.2Anitschkow NN.

A history of experimentation on arterial atherosclerosis in animals. In. Lumenthal HT, ed. Cowdryâs Arteriosclerosis. A Survey of the Problem.

Springfield, IL. Charles C Thomas. 1967. P21â44.3Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease.

The Framingham Study. Ann Epidemiol 1992;2:23â28.4Velasco JA. After 4S, CARE and LIPIDâis evidence-based medicine being practised?. Atherosclerosis 1999;147 Suppl 1:S39âS44.5Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis.

J Clin Invest 1991;88:1785â1792.6Tanner FC, Noll G, Boulanger CM, LÃ¼scher TF. Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries. Role of scavenger receptor and endothelium-derived nitric oxide. Circulation 1991;83:2012â2020.7LÃ¼scher TF, Landmesser U, von Eckardstein A, Fogelman AM. High-density lipoprotein.

Vascular protective effects, dysfunction, and potential as therapeutic target. Circ Res 2014;114:171â182.8Speer T, Rohrer L, Blyszczuk P, Shroff R, Kuschnerus K, KrÃ¤nkel N, Kania G, Zewinger S, Akhmedov A, Shi Y, Martin T, Perisa D, Winnik S, MÃ¼ller MF, Sester U, Wernicke G, Jung A, Gutteck U, Eriksson U, Geisel J, Deanfield J, von Eckardstein A, LÃ¼scher TF, Fliser D, Bahlmann FH, Landmesser U. Abnormal high-density lipoprotein induces endothelial dysfunction via activation of Toll-like receptor-2. Immunity 2013;38:754â768.9Libby P, Loscalzo J, Ridker PM, Farkouh ME, Hsue PY, Fuster V, Hasan AA,, Amar S. Inflammation, immunity, and in atherothrombosis.

JACC Review Topic of the Week. J Am Coll Cardiol 2018;72:2071â2081.10Maier W., Altwegg LA, Corti R, Gay S, Hersberger M, Maly FE, Sutsch G, Roffi M, Neidhart M, Eberli FR, Tanner FC, Gobbi S, von Eckardstein A, Luscher TF. Inflammatory markers at the site of ruptured plaque in acute myocardial infarction. Locally increased interleukin-6 and serum amyloid A but decreased C-reactive protein. Circulation 2005;111:1355â1361.11Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A.

The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994;331:417â424.12Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836â843.13Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AMJr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

N Engl J Med 2008;359:2195â2207.14Wyss CA, Neidhart M, Altwegg L, Spanaus KS, Yonekawa K, Wischnewsky MB, Corti R, Kucher N, Roffi M, Eberli FR, Amann-Vesti B, Gay S, von Eckardstein A, LÃ¼scher TF, Maier W. Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes. Eur Heart J 2010;31:1457â1469.15Heusch G, Gersh BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion. A continual challenge.

Eur Heart J 2017;38:774â784.16Westman PC, Lipinski MJ, Luger D, Waksman R, Bonow RO, Wu E, Epstein SE. Inflammation as a driver of adverse left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 2016;67:2050â2060.17Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119â1131.18Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ.

Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab. A secondary analysis from the CANTOS randomised controlled trial. Lancet 2018;391:319â328.19Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ. Effect of interleukin-1Î² inhibition with canakinumab on incident lung cancer in patients with atherosclerosis. Exploratory results from a randomised, double-blind, placebo-controlled trial.

Lancet 2017;390:1833â1842.20Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, LÃ³pez-SendÃ³n J, Ostadal P, Koenig W, Angoulvant D, GrÃ©goire JC, Lavoie MA, DubÃ© MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, LâAllier PL, Guertin MC, Roubille F. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med 2019;381:2497â2505.21Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R, Berry C, Koenig W, Lopez-Sendon J, Gamra H, Kiwan GS, Blondeau L, Orfanos A, Ibrahim R, GrÃ©goire JC, DubÃ© MP, Samuel M, Morel O, Lim P, Bertrand OF, Kouz S, Guertin MC, LâAllier PL, Roubille F. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J 2020;41:4092â4099.22Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH.

Update on colchicine, 2017. Rheumatology 2018;57(suppl_1):i4âi11.23Chia EW, Grainger R, Harper JL. Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis. A rationale for use of lowâdose colchicine. Br J Pharmacol 2009;153:1288â1295.24Wiendels NJ, Knuistingh Neven A, Rosendaal FR, Spinhoven P, Zitman FG, Assendelft WJ, Ferrari MD.

Chronic frequent headache in the general population. Prevalence and associated factors. Cephalalgia 2006;26:1434â1442.25MÃ¼hlhauser I, Sawicki PT, Blank M, Overmann H, Bender R, Berger M. Prognosis of persons with type 1 diabetes on intensified insulin therapy in relation to nephropathy. J Intern Med 2000;248:333â341.26Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P.

Risk of myocardial infarction and stroke after acute or vaccination. N Engl J Med 2004;351:2611â2618.27Liuzzo G, Biasucci LM, Gallimore JR, Caligiuri G, Buffon A, Rebuzzi AG, Pepys MB, Maseri A. Enhanced inflammatory response in patients with preinfarction unstable angina. J Am Coll Cardiol 1999;34:1696â1703. Published on behalf of the European Society of Cardiology.

All rights reserved. Â© The Author(s) 2020. For permissions, please email. Journals.permissions@oup.com.The Green Lane Cardiovascular Research Unit and The Green lane Coordinating Centre in Auckland New ZealandThe Green Lane Cardiovascular Research Unit (CVRU) was formed when Harvey White returned to Green Lane Hospital, Auckland, New Zealand from Boston in 1984 where he was a research fellow at the Brigham and Womenâs Hospital. While in Boston, he somehow gained the âgeneâ for research and writing.

Green Lane was the hospital where Sir Brian Barrett-Boyes and many colleagues had performed pioneering homograft aortic valve replacements and developed techniques of hypothermia for operating on babies with congenital heart disease. There was a focus on high quality clinical care and research.The mission of the CVRU was âto do research for improving patient care throughout the worldâ. The unit began research for three reasons. To improve patient care, to improve science, and to have fun. From the beginning, the unit undertook both local and international collaborative trials.

Local trials were very important. Between 1987 and 1989, there were three major publications from local trials. One in 1987 was in Circulation on âLeft ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarctionâ1 which Dr Eugene Braunwald has called one of the greatest advancements in post-MI management (Braunwald ACC 2013). And two were in the New England Journal of Medicine on thrombolysis and left ventricular function with comparison of streptokinase with placebo, and streptokinase with TPA.2,3It was very clear from the beginning that to make a difference to patient care, large numbers of patients (1000âs) would be needed, to have the statistical power to show benefits and to be able to assess harm. The only way of doing that was to collaborate, collaborate, and collaborate.International collaboration was first with Australia with Dr Phil Aylward.

Phil is an outstanding clinician who brings enormous clinical experience to steering committees in the design and practical undertaking of trials and played a major part in the HERO (Hirulog Early Reperfusion/Occlusion) Trials. And secondly, with Dr Andrew Tonkin and Dr John Simes, also from Australia, on the LIPID (Long-Term Intervention With Pravastatin in Ischaemic Disease) groupâa trial showing that pravastatin reduced total mortality in patients with previous myocardial infarction or unstable angina.4 New Zealand contributed over 3000 patients and the collaboration continues with over 20âyears follow-up and over 60 publications. The group also published the first study on prevention of stroke subtypes with statin therapy.5In 1988, an international trial branch was formed as part of CVRU to participate in International trials including the ISIS and Gusto trials. This was initially led by Maggie Scott, former charge nurse of the CCU at Green Lane Hospital. Maggie also coordinated the world-wide HERO-2 trial with 15 000 patients in 27 countries comparing bivalirudin with unfractionated heparin following fibrinolytic therapy6 (Figure 1).

Figure 1The Cardiovascular Research Unit (CVRU) in 1992.Figure 1The Cardiovascular Research Unit (CVRU) in 1992.In 2003, an Academic Research Organisation (ARO) named Green Lane Coordinating Centre Limited (GLCC) was formed offsite from Green Lane Hospital. Olga Bucan from Slovenia was the Director and coordinated the STabilisation of Atherosclerotic plaque By Initiation of darapLadib TherapY (STABILITY) Trial with 15 000 patients in 38 countries.7Dr John French joined as a Senior Cardiologist and Researcher in 1992. John is an enormously hard worker and has numerous publications on coronary flow, LV function, and survival as well as a seminal paper on the importance of factor V Leiden in young patients who had had an MI with normal coronary arteries.8 John left for Australia in 2003 but still closely collaborates on trials and registries.Dr Cheuk-Kit Wong joined CVRU in 1999 and published 25 papers on ECGs from the HERO ECG core laboratory including the first study to show that Q waves on an ECG are more important than door to reperfusion time for prognosis.9The CVRU is now based at Auckland City Hospital as part of the Green Lane Cardiovascular Department. The research unit continues to deliver excellent clinical trial management. A team of investigators, nurses, and administrators support the current trials which include a mix of international academic and pharmaceutical trials as well as local investigators with national and Auckland Hospital based studies (Figure 2 Group).

Figure 2The Cardiovascular Research Unit (CVRU) in 2020. Standing from L to R. Dr Jithendra Somaratne, Prof Harvey White, Dr Jocelyne Benatar, Prof Ralph Stewart. Sitting from L to R. Michelle DâSouza, Leah Howell, Cathrine Patten, and Diana Gatland.Figure 2The Cardiovascular Research Unit (CVRU) in 2020.

Standing from L to R. Dr Jithendra Somaratne, Prof Harvey White, Dr Jocelyne Benatar, Prof Ralph Stewart. Sitting from L to R. Michelle DâSouza, Leah Howell, Cathrine Patten, and Diana Gatland.Dr Jocelyne Benatar joined in 2000 and has done a number of studies assessing the effects of dairy food on cardiovascular disease and diet on cardiometabolic syndrome.10 She continues as the principal and co-investigator for a number of nutritional, diabetes, rehabilitation, and cardiovascular trials.Dr Ralph Stewart joined CVRU in 1999 and GLCC in 2003 and has led numerous trials including the recent New Zealand Oxygen Study (Stewart ESC 2019). He along with Ivor Gerber reported the relationship between NT-proBNP levels and the prognosis of patients with aortic valve disease.11Research nurses have been a very important and an integral part of the CVRU and the development of a career pathway and work/life balance has been a primary focus.

The CVRU was one of the first to employ research nurses. The first research nurse was Barbara Williams who had been in charge of the CCU at Green Lane Hospital. Barbara led a study on consent in patient with acute STEMI published in the Lancet.12 Mary Denton was CVRUâs first nurse manager. Today, nurse co-ordinator Cathrine Patten manages the current trials.Caroline Alsweiler who was a Senior Clinical Research Associate and Clinical Trial Manager became Director of GLCC in 2014. The GLCC works closely with a core group of investigators in New Zealand, Australia, Singapore, Hong Kong, Malaysia, Thailand, Korea, and the Philippines to deliver high quality data (Figure 3), The Mission statement is âto improve the health and quality of life of people throughout the world through innovative clinical researchâ.

Together with support from national and international academia, they are dedicated to achieving the highest possible standard in clinical research while maintaining well-established relationships with investigators both nationally and internationally, achieving quick turnaround times for completion of regulatory documents, and ensuring integrity of research data. The GLCC has been involved with over 70 international clinical trials from Phases IIâIV. Figure 3Members of the Green Lane Coordinating Centre (GLCC) in 2019.Figure 3Members of the Green Lane Coordinating Centre (GLCC) in 2019.The CVRU and GLCC have received many acknowledgements and awards. It has to be strongly stressed that these and publications have been a team effort. In 1998, Harvey was awarded the Prince Mahidol Award for Medicine by the King of Thailand for introducing aspirin and fibrinolytic therapy in 27 developing countries, including China (Figure 4).

This award is considered the Nobel Prize of the East and is given for introducing treatments rather than being the first to discover something. Harvey was bestowed a Matai (Chief) title in Samoa in 1994 with a title of âLaâauliâ the highest peak in the land for his work treating patients as well as working with WHO in Samoa. Figure 4Harvey receiving the Prince Mahidol Award from the King of Thailand.Figure 4Harvey receiving the Prince Mahidol Award from the King of Thailand.In 2020, the work from CVRU and GLCC was ranked no. 5 in the world across all branches of medicine for publication of RCT-related articles in high-impact-factor medical journals over the past five decades and with the highest collaboration index.13The CVRU and GLCC continue to be very productive with over 20 ongoing trials. The special research interests include management of acute coronary syndromes, antithrombotic management of acute coronary syndromes and atrial fibrillation, biomarkers, secondary prevention of cardiovascular disease, management of cardiovascular disease in the elderly, diabetes, nutrition, rehabilitation, frailty, dyslipidaemia, and registry studies.Over 1000 peer-reviewed manuscripts have been published.

Contributions of the two organizations to multicentre trials have helped develop the evidence base for guidelines for the practice of clinical cardiology. These include the role of troponins in ACS,14 the importance of 0.5âmm ST depression for prognosis in patients with non-STEMI,15 elderly patients should not be denied fibrinolytic therapy,16 the risks of switching antithrombotic therapy,17 the BARC bleeding definition,18 and the Universal definition of MI defining the five types of MI.19Relationships have been very important and one of the wonderful things about collaborating in International trials is meeting and making friends with the most amazing people from the ISIS, Gusto, TIMI, Duke, Leuven, Uppsala, Vigour, ECLA, OASIS, New York University, Montreal, SAMHRI, ODYSSEY, and Cleveland Clinic groups etc. (Figure 5). Figure 5Members of the Vigour organization at the Uppsala Research Centre from Duke USA, Canada, Sweden, and New Zealand in Uppsala in 2010.Figure 5Members of the Vigour organization at the Uppsala Research Centre from Duke USA, Canada, Sweden, and New Zealand in Uppsala in 2010.A MÄori proverb (of the indigenous people of New Zealand) says:âHe aha te mea nui o te aoWhat is the most important thing in the world?. He tangata, he tangata, he tangataIt is the people, it is the people, it is the peopleâThe many people in the two Green Lane organizations (CVRU and GLCC) have had fun, perhaps contributions have been made to science and patient care has also been improved.

AcknowledgementsMichelle D'Souza provided editorial and secretarial assistance in the preparation of the manuscript and was funded by The Green Lane Research and Educational Fund (GLREF), Auckland City Hospital. Dr White gratefully thanks the GLREF for support as the John Neutze Fellow. We would like to thank cardiologists and cardiac surgeons and nurses throughout New Zealand and the world, and patients who have taken part in the clinical trials.Conflict of interest. H.D.W. Has received grant support paid to the institution and fees for serving on a steering committee from Sanofi-Aventis and Regeneron Pharmaceuticals, for the HEART-FID study from American Regent.

For the dal-GenE study from DalCor Pharma UK Inc., for the AEGIS-II study from CSL Behring, for the SCORED trial and the SOLOIST-WHF trial from Sanofi-Aventis Australia Pty Ltd, and for the CLEAR Outcomes Study from Esperion Therapeutics Inc. He was on an Advisory Board for Genentech, Inc. And received lecture fees from AstraZeneca outside the submitted work. ReferencesReferences are available as supplementary material at European Heart Journal online. Published on behalf of the European Society of Cardiology.

ÂListen to the podcast associated with this article, which can also be found at ESC CardioTalk https://www.escardio.org/The-ESC/Whatwe-do/news/ESC-Cardio-Talk This editorial refers to âTime-to-treatment initiation of colchicine and cardiovascular outcomes buy lasix tablets after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)ââ , by N. Bouabdallaoui et al., on page 4092. Virchowâs prophecyThe late Rudolf buy lasix tablets L.C. Virchow (1821â1902) made a visionary statement when he wrote in one of his textbooks âAtherosclerosis is a chronic inflammation induced by cholesterolâ.1 It did not have much impact for several decades until the Russian scientist Nikolay Nikolaevich Anichkov (1885â1964) showed in his seminal experiments in the rabbit aorta that a high fat diet induces cholesterol-rich plaques.2 Thereafter, research focused on cholesterol rather than inflammation, with crucial epidemiological studies in Framingham and worldwide confirming an association of plasma lipid levels with the complications of atherosclerosis, i.e.

Myocardial infarction, stroke, and sudden and premature death.3 The final proof of the cholesterol hypothesis came with the 4S trial using simvastatin in patients with coronary artery disease, demonstrating an impressive reduction of major cardiovascular events with pharmacological cholesterol lowering.4 Rediscovering inflammationHowever, there was a remaining cardiovascular risk, and this led to the rediscovery of the true buy lasix tablets meaning of Virchowâs seminal statement. First of all, it appeared from experimental studies that oxidized or otherwise modified cholesterol rather than native LDL-cholesterol (LDL-C)5,6 was involved and that dysfunctional HDL-C lost its protective function.7,8 The expression of adhesion molecules and, in turn, the presence of white blood cells such as monocytes, macrophages, and T cells in atherosclerotic plaques9 and the occluding thrombus in acute coronary syndromes (ACS)10 further corroborated the concept that inflammation might play a role. In 1994, the group of Attilio Maseris showed that acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) predicted future cardiovascular events in patients with unstable angina.11 This observation was soon extended by Charles Hennekens and Paul Ridker to healthy individuals.12 In individuals at high cardiovascular risk with elevated CRP, buy lasix tablets but normal or midly elevated cholesterol, rosuvastatin lowered not only CRP, but also major cardiovascular events (MACE).13 Indeed, a mild anti-inflammatory action of statins had previously been demonstrated in small experimental trials. Thus, Virchowâs vision was indeed prophetic.

However, how can this information be used clinically to the benefit of patients?. Inflammation and acute coronary syndromesA patient population in which inflammation is particularly buy lasix tablets important are those with ACS. Indeed, at the time of such an acute event, CRP and SAA plasma levels are several magnitudes higher than in patients with chronic coronary syndromes.10 Thus, it seems that ACS are associated with an inflammatory burst. Of note, inflammation is particularly high at the site of acute coronary occlusion, with an array of cytokines expressed, among them interleukins10 acting on Toll-like receptors on white blood cells in a vicious cycle leading to an acute inflammatory storm.14 In this context, inflammation is a major trigger of plaque vulnerability, erosion, or rupture, buy lasix tablets and eventually coronary occlusion.

After reperfusion, as occurs after successful primary percutaneous coronary intervention, inflammation importantly contributes to reperfusion injury also in the myocardium15 and in turn increases infarct size and scar formation, leading to left ventricular remodelling16 and MACE. Anti-inflammatory therapy as a new strategyBased on these data and insights buy lasix tablets into the molecular mechanisms of ACS, inflammation became the new therapeutic frontier. After a few smaller proof-of-concept studies, the CANTOS trial using the interleukin-1Î² (IL-Î²) antagonist canakinumab proved the causal association of inflammation with MACE after ACS.17 Indeed, after 4 years, canakinumab reduced MACE (i.e. Non-fatal myocardial infarction or stroke and cardiovascular death) overall by â¼15% 17 and by 26% in those with an on-treatment CRP level <2 mg/L.18 Interestingly, canakinumab also reduced the occurrence of cancer, and in particular lung cancer, in these patients.19 The latter finding led the sponsor Novartis to decide to develop canakinumab for this indication rather than in cardiac patients.Thus, at this point, the clinical implementation buy lasix tablets of anti-inflammation came to a halt until recently when the results of the COLCOT trial were published.

In this trial, patients who had survived an ACS were randomized within 30 days after the event to either placebo or colchicine at a low dose of 0.5 mg daily and were followed-up for a median of 2 years.20 Impressively, colchicine led to a 23% reduction of the primary endpoint of death, rescucitated cardiac arrest, ACS, stroke, and urgent hospitalization for angina requiring revascularization (however with the latter beiing the primary driver of the effect). Given the early inflammatory burst at the time of ACS, it remained unclearâas has been the case in CANTOSâwhether very early anti-inflammation might be even more advantageous or possibly rather dangerous. This question buy lasix tablets has now been addressed in the manuscript by Bouabdallaoui et al. In the current issue of the European Heart Journal.21 They grouped the patients enrolled in COLCOT into three groups that had received investigational drugs (i.e.

Colchicine or placebo) within the buy lasix tablets first 3, 4â7, or 8 or more days. Importantly, after a mean follow-up of 23 months, there was an amazing significant reduction of 48% in the primary endpoint in those receiving colchicine within 3 days or less, but only of 4â18% in those receiving the drug at a later timepoint. Thus, anti-inflammatory buy lasix tablets therapy seems to work best the sooner it is provided after ACS. Given the fact that inflammation is most pronounced in the very early phase of an acute myocardial infarction, these results make a lot of sense.

Learning from goutWhat might be the mechanism of action of colchicine which buy lasix tablets traditionally is used in the management of gout?. The mechanisms of action of colchicine are obviously multiple and not completely understood.22 First of all, colchicine binds to free tubulin, an Î±Î² heterodimer initially identified as the cellular colchicine-binding protein that forms microtubules upon polymerization and interacts with many regulatory cellular proteins (Figure 1). Thereby colchicine inhibits cell migration and cytokine release, particularly by white blood cells. Colchicine also modulates superoxide production buy lasix tablets by leucocytes23 which is in part responsible for the inhibition of neutrophil adhesion, extravasation, and recruitment by altering neutrophil L-selectin expression and endothelial cell E-selectin distribution, and suppressing the release of the chemotactic leukotriene B4.

Whether all of these effects are secondary to the impact of colchicine on microtubules remains to be determined. Importantly, however, colchicine inhibits the Nod-Like Receptor Protein 3 (NLRP3) inflammasome (while urate crystals activate i)t,24 thereby suppressing caspase-1 buy lasix tablets activation and the subsequent release of IL-1Î² and IL-18. Figure 1). As the NLRP3 inflammasome is expressed in the myeloid lineage,25 buy lasix tablets colchicine appears to mainly interfere with neutrophils and monocytes and macrophages, i.e.

The innate immune system that is involved in ACS, rather than the adaptive immune system. Figure buy lasix tablets 1Molecular effects of colchicine in white blood cells via tubulin and microtubuli as well as Nod-Like Receptor Protein 3 (NLRP3) inflammasome. Inset left, urate crystals. Inset right, cholesterol crystals (modified from Imazio M, Gaita F.

Heart April 2016 Vol 102 No 8).Figure 1Molecular effects of colchicine in white blood cells via tubulin and microtubuli as well buy lasix tablets as Nod-Like Receptor Protein 3 (NLRP3) inflammasome. Inset left, urate crystals. Inset right, cholesterol buy lasix tablets crystals (modified from Imazio M, Gaita F. Heart April 2016 Vol 102 No 8).

Colchicine after acute buy lasix tablets coronary syndromes?. Should we now use colchicine in the very early phase of ACS as a remedy to reduce MACE?. First of all, colchicine is cheap and, particularly at the low dose used buy lasix tablets in COLCOT, relatively well tolerated. Indeed, in the COLCOT trial, gastrointestinal side effects such as nausea and flatulence were quite rare, with 2.4% vs.

1.2% with placebo. Obviously, as any anti-inflammatory drug, buy lasix tablets colchicine increases the risk of . Pneumonia was rare, but indeed more common, with 0.9% vs. 0.4% with colchicine and buy lasix tablets placebo, respectively.

Should we therefore avoid prescribing colchicine for the elderly who are at risk of pneumonia or provide them with pneumococcal vaccination?. Indeed, acute s may precipitate buy lasix tablets myocardial infarction, while influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in this risk, but may actually be protective.26 As such, this may be a reasonable precaution in this context.A second question is whether colchicine would be suitable for all ACS patients or only for those with signs of excessive inflammation?. Indeed, not all patients with ACS have signs of inflammation. Typically, out-of-the-blue infarctions are triggered by other stimuli (such as shear stress, pulsatility, spasm, etc.), while in heralded infarction inflammation plays a primary role.10,27 Unfortunatly, CRP or SAA were not assessed in COLCOT and hence a more personalized use of this drug awaits further studies.

Overall, however, the main COLCOT trial and now this important subanalysis buy lasix tablets open the door for an even more effective treatment of patients with ACS with remaining inflammatory risk.Conflict of interest. There are no conflicts of interest for this Editorial. However, the author has received grants for buy lasix tablets his ACS research from Amgen, AstraZeneca, Eli Lilly, Medtronic, and Sanofi, and honoraria for consulting and lecturing from Amgen and Sanofi.The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. References1Virchow R.

Die Cellularpathologie in ihrer BegrÃ¼ndung auf buy lasix tablets physiologische und pathologische Gewebelehre A. Berlin. Hirschwald. 1858.2Anitschkow NN.

A history of experimentation on arterial atherosclerosis in animals. In. Lumenthal HT, ed. Cowdryâs Arteriosclerosis.

A Survey of the Problem. Springfield, IL. Charles C Thomas. 1967.

P21â44.3Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease. The Framingham Study. Ann Epidemiol 1992;2:23â28.4Velasco JA.

After 4S, CARE and LIPIDâis evidence-based medicine being practised?. Atherosclerosis 1999;147 Suppl 1:S39âS44.5Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991;88:1785â1792.6Tanner FC, Noll G, Boulanger CM, LÃ¼scher TF.

Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries. Role of scavenger receptor and endothelium-derived nitric oxide. Circulation 1991;83:2012â2020.7LÃ¼scher TF, Landmesser U, von Eckardstein A, Fogelman AM. High-density lipoprotein.

Inflammation, immunity, and in atherothrombosis. JACC Review Topic of the Week. J Am Coll Cardiol 2018;72:2071â2081.10Maier W., Altwegg LA, Corti R, Gay S, Hersberger M, Maly FE, Sutsch G, Roffi M, Neidhart M, Eberli FR, Tanner FC, Gobbi S, von Eckardstein A, Luscher TF. Inflammatory markers at the site of ruptured plaque in acute myocardial infarction.

Locally increased interleukin-6 and serum amyloid A but decreased C-reactive protein. Circulation 2005;111:1355â1361.11Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994;331:417â424.12Ridker PM, Hennekens CH, Buring JE, Rifai N.

C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836â843.13Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AMJr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195â2207.14Wyss CA, Neidhart M, Altwegg L, Spanaus KS, Yonekawa K, Wischnewsky MB, Corti R, Kucher N, Roffi M, Eberli FR, Amann-Vesti B, Gay S, von Eckardstein A, LÃ¼scher TF, Maier W.

Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes. Eur Heart J 2010;31:1457â1469.15Heusch G, Gersh BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion. A continual challenge.

N Engl J Med 2017;377:1119â1131.18Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab. A secondary analysis from the CANTOS randomised controlled trial. Lancet 2018;391:319â328.19Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ.

Effect of interleukin-1Î² inhibition with canakinumab on incident lung cancer in patients with atherosclerosis. Exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 2017;390:1833â1842.20Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, LÃ³pez-SendÃ³n J, Ostadal P, Koenig W, Angoulvant D, GrÃ©goire JC, Lavoie MA, DubÃ© MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, LâAllier PL, Guertin MC, Roubille F. Efficacy and safety of low-dose colchicine after myocardial infarction.

N Engl J Med 2019;381:2497â2505.21Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R, Berry C, Koenig W, Lopez-Sendon J, Gamra H, Kiwan GS, Blondeau L, Orfanos A, Ibrahim R, GrÃ©goire JC, DubÃ© MP, Samuel M, Morel O, Lim P, Bertrand OF, Kouz S, Guertin MC, LâAllier PL, Roubille F. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J 2020;41:4092â4099.22Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH. Update on colchicine, 2017.

Rheumatology 2018;57(suppl_1):i4âi11.23Chia EW, Grainger R, Harper JL. Colchicine suppresses neutrophil superoxide production in a murine model of gouty arthritis. A rationale for use of lowâdose colchicine. Br J Pharmacol 2009;153:1288â1295.24Wiendels NJ, Knuistingh Neven A, Rosendaal FR, Spinhoven P, Zitman FG, Assendelft WJ, Ferrari MD.

J Intern Med 2000;248:333â341.26Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute or vaccination. N Engl J Med 2004;351:2611â2618.27Liuzzo G, Biasucci LM, Gallimore JR, Caligiuri G, Buffon A, Rebuzzi AG, Pepys MB, Maseri A. Enhanced inflammatory response in patients with preinfarction unstable angina.

For permissions, please email. Journals.permissions@oup.com.The Green Lane Cardiovascular Research Unit and The Green lane Coordinating Centre in Auckland New ZealandThe Green Lane Cardiovascular Research Unit (CVRU) was formed when Harvey White returned to Green Lane Hospital, Auckland, New Zealand from Boston in 1984 where he was a research fellow at the Brigham and Womenâs Hospital. While in Boston, he somehow gained the âgeneâ for research and writing. Green Lane was the hospital where Sir Brian Barrett-Boyes and many colleagues had performed pioneering homograft aortic valve replacements and developed techniques of hypothermia for operating on babies with congenital heart disease.

There was a focus on high quality clinical care and research.The mission of the CVRU was âto do research for improving patient care throughout the worldâ. The unit began research for three reasons. To improve patient care, to improve science, and to have fun. From the beginning, the unit undertook both local and international collaborative trials.

The only way of doing that was to collaborate, collaborate, and collaborate.International collaboration was first with Australia with Dr Phil Aylward. Phil is an outstanding clinician who brings enormous clinical experience to steering committees in the design and practical undertaking of trials and played a major part in the HERO (Hirulog Early Reperfusion/Occlusion) Trials. And secondly, with Dr Andrew Tonkin and Dr John Simes, also from Australia, on the LIPID (Long-Term Intervention With Pravastatin in Ischaemic Disease) groupâa trial showing that pravastatin reduced total mortality in patients with previous myocardial infarction or unstable angina.4 New Zealand contributed over 3000 patients and the collaboration continues with over 20âyears follow-up and over 60 publications. The group also published the first study on prevention of stroke subtypes with statin therapy.5In 1988, an international trial branch was formed as part of CVRU to participate in International trials including the ISIS and Gusto trials.

This was initially led by Maggie Scott, former charge nurse of the CCU at Green Lane Hospital. Maggie also coordinated the world-wide HERO-2 trial with 15 000 patients in 27 countries comparing bivalirudin with unfractionated heparin following fibrinolytic therapy6 (Figure 1). Figure 1The Cardiovascular Research Unit (CVRU) in 1992.Figure 1The Cardiovascular Research Unit (CVRU) in 1992.In 2003, an Academic Research Organisation (ARO) named Green Lane Coordinating Centre Limited (GLCC) was formed offsite from Green Lane Hospital. Olga Bucan from Slovenia was the Director and coordinated the STabilisation of Atherosclerotic plaque By Initiation of darapLadib TherapY (STABILITY) Trial with 15 000 patients in 38 countries.7Dr John French joined as a Senior Cardiologist and Researcher in 1992.

John is an enormously hard worker and has numerous publications on coronary flow, LV function, and survival as well as a seminal paper on the importance of factor V Leiden in young patients who had had an MI with normal coronary arteries.8 John left for Australia in 2003 but still closely collaborates on trials and registries.Dr Cheuk-Kit Wong joined CVRU in 1999 and published 25 papers on ECGs from the HERO ECG core laboratory including the first study to show that Q waves on an ECG are more important than door to reperfusion time for prognosis.9The CVRU is now based at Auckland City Hospital as part of the Green Lane Cardiovascular Department. The research unit continues to deliver excellent clinical trial management. A team of investigators, nurses, and administrators support the current trials which include a mix of international academic and pharmaceutical trials as well as local investigators with national and Auckland Hospital based studies (Figure 2 Group). Figure 2The Cardiovascular Research Unit (CVRU) in 2020.

He along with Ivor Gerber reported the relationship between NT-proBNP levels and the prognosis of patients with aortic valve disease.11Research nurses have been a very important and an integral part of the CVRU and the development of a career pathway and work/life balance has been a primary focus. The CVRU was one of the first to employ research nurses. The first research nurse was Barbara Williams who had been in charge of the CCU at Green Lane Hospital. Barbara led a study on consent in patient with acute STEMI published in the Lancet.12 Mary Denton was CVRUâs first nurse manager.

Today, nurse co-ordinator Cathrine Patten manages the current trials.Caroline Alsweiler who was a Senior Clinical Research Associate and Clinical Trial Manager became Director of GLCC in 2014. The GLCC works closely with a core group of investigators in New Zealand, Australia, Singapore, Hong Kong, Malaysia, Thailand, Korea, and the Philippines to deliver high quality data (Figure 3), The Mission statement is âto improve the health and quality of life of people throughout the world through innovative clinical researchâ. Together with support from national and international academia, they are dedicated to achieving the highest possible standard in clinical research while maintaining well-established relationships with investigators both nationally and internationally, achieving quick turnaround times for completion of regulatory documents, and ensuring integrity of research data. The GLCC has been involved with over 70 international clinical trials from Phases IIâIV.

Figure 3Members of the Green Lane Coordinating Centre (GLCC) in 2019.Figure 3Members of the Green Lane Coordinating Centre (GLCC) in 2019.The CVRU and GLCC have received many acknowledgements and awards. It has to be strongly stressed that these and publications have been a team effort. In 1998, Harvey was awarded the Prince Mahidol Award for Medicine by the King of Thailand for introducing aspirin and fibrinolytic therapy in 27 developing countries, including China (Figure 4). This award is considered the Nobel Prize of the East and is given for introducing treatments rather than being the first to discover something.

Harvey was bestowed a Matai (Chief) title in Samoa in 1994 with a title of âLaâauliâ the highest peak in the land for his work treating patients as well as working with WHO in Samoa. Figure 4Harvey receiving the Prince Mahidol Award from the King of Thailand.Figure 4Harvey receiving the Prince Mahidol Award from the King of Thailand.In 2020, the work from CVRU and GLCC was ranked no. 5 in the world across all branches of medicine for publication of RCT-related articles in high-impact-factor medical journals over the past five decades and with the highest collaboration index.13The CVRU and GLCC continue to be very productive with over 20 ongoing trials. The special research interests include management of acute coronary syndromes, antithrombotic management of acute coronary syndromes and atrial fibrillation, biomarkers, secondary prevention of cardiovascular disease, management of cardiovascular disease in the elderly, diabetes, nutrition, rehabilitation, frailty, dyslipidaemia, and registry studies.Over 1000 peer-reviewed manuscripts have been published.

He tangata, he tangata, he tangataIt is the people, it is the people, it is the peopleâThe many people in the two Green Lane organizations (CVRU and GLCC) have had fun, perhaps contributions have been made to science and patient care has also been improved. AcknowledgementsMichelle D'Souza provided editorial and secretarial assistance in the preparation of the manuscript and was funded by The Green Lane Research and Educational Fund (GLREF), Auckland City Hospital. Dr White gratefully thanks the GLREF for support as the John Neutze Fellow. We would like to thank cardiologists and cardiac surgeons and nurses throughout New Zealand and the world, and patients who have taken part in the clinical trials.Conflict of interest.

H.D.W. Has received grant support paid to the institution and fees for serving on a steering committee from Sanofi-Aventis and Regeneron Pharmaceuticals, for the HEART-FID study from American Regent. For the dal-GenE study from DalCor Pharma UK Inc., for the AEGIS-II study from CSL Behring, for the SCORED trial and the SOLOIST-WHF trial from Sanofi-Aventis Australia Pty Ltd, and for the CLEAR Outcomes Study from Esperion Therapeutics Inc. He was on an Advisory Board for Genentech, Inc.

And received lecture fees from AstraZeneca outside the submitted work. ReferencesReferences are available as supplementary material at European Heart Journal online. Published on behalf of the European Society of Cardiology. All rights reserved.

Â© The Author(s) 2020. For permissions, please email. Journals.permissions@oup.com..

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About This TrackerThis tracker provides the number of confirmed cases and deaths from novel hypertension digoxin lasix by country, the trend in confirmed case and death counts by country, and a global map showing which countries have confirmed cases and deaths. The data are drawn from the Johns Hopkins University (JHU) hypertension Resource Centerâs hypertension medications Map and the World Health Organizationâs (WHO) hypertension Disease (hypertension medications-2019) situation reports.This tracker will be updated regularly, as new data are released.Related Content. About hypertension medications digoxin lasix hypertensionIn late 2019, a new hypertension emerged in central China to cause disease in humans. Cases of this disease, known as hypertension medications, have since been reported across around the globe. On January 30, 2020, the World Health Organization (WHO) declared the lasix represents a public health emergency of digoxin lasix international concern, and on January 31, 2020, the U.S.

Department of Health and Human Services declared it to be a health emergency for the United States..

About This TrackerThis tracker provides the number of confirmed cases buy lasix tablets and deaths from novel hypertension by country, the trend in confirmed case and death counts by country, and a global map showing which countries have confirmed cases what is the cost of lasix and deaths. The data are drawn from the Johns Hopkins University (JHU) hypertension Resource Centerâs hypertension medications Map and the World Health Organizationâs (WHO) hypertension Disease (hypertension medications-2019) situation reports.This tracker will be updated regularly, as new data are released.Related Content. About hypertension medications hypertensionIn late buy lasix tablets 2019, a new hypertension emerged in central China to cause disease in humans. Cases of this disease, known as hypertension medications, have since been reported across around the globe.

On January 30, 2020, the World Health Organization (WHO) declared the lasix represents a public health emergency of international buy lasix tablets concern, and on January 31, 2020, the U.S. Department of Health and Human Services declared it to be a health emergency for the United States..

Lasix to remove fluid in lungs

The hypertension medications lasix continues lasix to remove fluid in lungs to negatively impact population health by indirect effects on patient and healthcare systems, in addition to my sources the direct effects of hypertension medications itself. Accurate and quantitative information about the indirect effects of the hypertension medications lasix on cardiovascular disease (CVD) services and outcomes will allow better public health planning. Ball and lasix to remove fluid in lungs colleagues1 aim to âdesign and implement a simple tool for monitoring and visualising trends in CVD hospital services in the UKâ and towards that end they present pilot data from a preliminary cohort of nine UK hospitals in this issue of Heart. Comparing 6 months in 2019â2020 (that include the hypertension medications lockdown in the UK) to the same time period in 2018â2019, there was a 57.9% decrease in total hospital admissions and a 52.9% decrease in emergency department visits (figure 1).

In addition, there was a 31%â88%âdecline during lockdown in procedures for treatment of cardiac, cerebrovascular and other vascular conditions.Overall hospital activity (admissions, ED attendances and hypertension medications admissions) between 31 October 2019 and 10 May 2020 compared with the same weeks from 2018 to 2019. Lines describe the mean hospital activities in 2019â2020 lasix to remove fluid in lungs (solid) and 2018â2019 (dotted). Shading represents 95%âCI of the respective hospital activity. The first case of hypertension medications was on 31 January 2020 and lockdown started on 23 March 2020.

ED, emergency department." data-icon-position data-hide-link-title="0">Figure 1 Overall hospital activity (admissions, ED attendances and hypertension medications admissions) between lasix to remove fluid in lungs 31 October 2019 and 10 May 2020 compared with the same weeks from 2018 to 2019. Lines describe the mean hospital activities in 2019â2020 (solid) and 2018â2019 (dotted). Shading represents 95%âCI of the respective hospital activity. The first case of hypertension medications was on 31 January 2020 and lockdown started lasix to remove fluid in lungs on 23 March 2020.

ED, emergency department.From the other side of the world, Brant and colleagues2 report the number of cardiovascular deaths in the six Brazilian cities with the greatest number of hypertension medications deaths. They conclude. ÂExcess cardiovascular mortality was greater in the less developed cities, possibly associated with healthcare lasix to remove fluid in lungs collapse. Specified cardiovascular deaths decreased in the most developed cities, in parallel with an increase in unspecified cardiovascular and home deaths, presumably as a result of misdiagnosis.

Conversely, specified cardiovascular deaths increased in cities with a healthcare collapseâ (figure 2).Per cent change with 95% CIs between the observed and expected number of deaths in 2020 for specified cardiovascular deaths (acute coronary syndromes and stroke) and unspecified cardiovascular diseases per selected six capital cities." data-icon-position data-hide-link-title="0">Figure 2 Per cent change with 95% CIs between the observed and expected number of deaths in 2020 for specified cardiovascular deaths (acute coronary syndromes and stroke) and unspecified cardiovascular diseases per selected six capital cities.In the accompanying editorial, Watkins3 notes that âTaken together, these two studies quantify what many readers of this journal have experienced firsthand. The restructuring of hospital services to cope with an influx of hypertension medications cases, combined with social distancing measures, has severely limited access to cardiovascular care, adversely impacting patient outcomes.â He then goes on to propose policy responses to reduce all-cause death among patients with CVD including deaths due to hypertension medications or to disruptions to healthcare delivery associated with the lasix (figure lasix to remove fluid in lungs 3). His two key messages are. (1) âthe global and national lasix responses cannot be separated from the cardiovascular health agendaâ and (2) âpriorities for cardiovascular science must pivot, capitalising on lessons learnt during the lasixâ.Critical elements of a comprehensive policy response to cardiovascular disease during hypertension medications.

The elements proposed above can be modified to fit the resource levels and lasix to remove fluid in lungs epidemiological contexts of different countries. Areas marked in red are those likely to translate into the largest short-term mortality gains. Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality." data-icon-position data-hide-link-title="0">Figure 3 Critical elements of a comprehensive policy response to cardiovascular disease during hypertension medications. The elements proposed above can be modified to fit the resource levels and epidemiological contexts of lasix to remove fluid in lungs different countries.

Areas marked in red are those likely to translate into the largest short-term mortality gains. Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality.Other interesting papers in this issue of Heart include a study by Doris and colleagues4 showing that in adults with aortic stenosis CT quantitation of valve calcification is reproducible and demonstrates a greater rate of change in disease severity, compared with echocardiography. Guzzetti and Clavel5 point out that more precise measures of aortic stenosis (AS) severity will allow smaller sample sizes in clinical trials of potential medical therapies, in addition to providing insights into the lasix to remove fluid in lungs pathophysiology of disease progression (figure 4).Model of AS progression. Pathophysiological model of serial AS progression (âaortic stenosis cascadeâ, in blue), along with imaging biomarkers targeting each phase (red) and potential disease-modifying treatments being currently tested in randomised clinical trials (green).

1South Korean PCSK9 inhibitors (NCT03051360). 2EAVaLL. Early aortic valve lipoprotein(a) lowering (NCT02109614). 3SALTIRE II.

Study investigating the effect of drugs used to treat osteoporosis on the progression of calcific aortic stenosis (NCT02132026). 4BASIK2. Bicuspid aortic valve stenosis and the effect of vitamin K2 on calcium metabolism on 18F-NaF PET/MRI (NCT02917525). 5EvoLVeD.

Early valve replacement guided by biomarkers of left ventricular decompensation in asymptomatic patients with severe AS (NCT03094143). 6Early TAVR. Evaluation of transcatheter aortic valve replacement compared with surveillance for patients with asymptomatic severe aortic stenosis (NCT03042104). 18F-FDG, 18-fluorodeoxyglucose.

18F-NaF, 18-sodium fluoride. AS, aortic stenosis. AVC, aortic valve calcification. PET, positron emission tomography.

PCSK9, proprotein convertase subtilisin/kexin type 9. TAVR, transcatheter aortic valve replacement." data-icon-position data-hide-link-title="0">Figure 4 Model of AS progression. Pathophysiological model of serial AS progression (âaortic stenosis cascadeâ, in blue), along with imaging biomarkers targeting each phase (red) and potential disease-modifying treatments being currently tested in randomised clinical trials (green). 1South Korean PCSK9 inhibitors (NCT03051360).

2EAVaLL. Early aortic valve lipoprotein(a) lowering (NCT02109614). 3SALTIRE II. Study investigating the effect of drugs used to treat osteoporosis on the progression of calcific aortic stenosis (NCT02132026).

4BASIK2. Bicuspid aortic valve stenosis and the effect of vitamin K2 on calcium metabolism on 18F-NaF PET/MRI (NCT02917525). 5EvoLVeD. Early valve replacement guided by biomarkers of left ventricular decompensation in asymptomatic patients with severe AS (NCT03094143).

6Early TAVR. Evaluation of transcatheter aortic valve replacement compared with surveillance for patients with asymptomatic severe aortic stenosis (NCT03042104). 18F-FDG, 18-fluorodeoxyglucose. 18F-NaF, 18-sodium fluoride.

AS, aortic stenosis. AVC, aortic valve calcification. PET, positron emission tomography. PCSK9, proprotein convertase subtilisin/kexin type 9.

TAVR, transcatheter aortic valve replacement.In a study of patients undergoing atrial fibrillation (AF) ablation, Piccini and colleagues6 found that almost 30% experienced recurrent atrial tachycardiac (AT) or AF within 3 months. However, although those without recurrent AT/AF had greater improvement in functional status, overall quality of life was similar in those with and without AT/AF recurrence. Sridhar and Colbert7 discuss the importance of patient-reported outcomes (PROs), not just âhardâ clinical endpoints in clinical trials. ÂAs researchers and clinicians, our goals must align with those of the patients and what they value.

It is heartening to see that more and more clinical trials in cardiology and electrophysiology are incorporating PROs as important endpoints. A slow but definite paradigm shift is occurring to incorporate therapies with a focus on improving patientsâ lives, not just their hearts.âThe Education in Heart article in this issue discusses the diagnosis and management of familial hypercholesterolemia.8 Our Cardiology in Focus article âWhat to do when things go wrongâ provides a thoughtful discussion of the key steps in dealing with medical error.9 The Image Challenge in this issue10 provides a concise review of a sophisticated set of possible diagnoses to consider in a patient with a new murmur and classic echocardiographic images. Be sure to look at our online Image Challenge archive with over 150 image-based multiple choice questions and answers (https://heart.bmj.com/pages/collections/image_challenges/).Global trends in cardiovascular health have reached a worrisome inflection point. Decades of innovation led to a slew of drugs, devices and programmes that translated into reduced mortality from cardiovascular diseases in many countries.

Unfortunately, progress on cardiovascular mortality since 2010 has slowed. In some countries, it has even reversed.1 Compounding the problem, political actions on cardiovascular health have been inadequate, and health systems across many low-income and middle-income countries are woefully under-resourced to scale up basic cardiovascular services. These factors could increase global health inequalities in coming decades.2hypertension medications threatens to derail progress on cardiovascular health even furtherCardiovascular practitioners are now under greater pressure to deliver the same or better care in the context of a lasix. hypertension medications has hit cardiovascular care particularly hard.

WHO surveys recently found that cardiovascular services have been partially or completely disrupted in nearly half of countries with community spread of hypertension medications, raising the chance of increased cardiovascular mortality in these locations.3Two studies published in this issue of Heart shed more light on the specific effects of hypertension medications on health systems in Brazil and the UK. Brant et al looked at cardiovascular mortality in six Brazilian capital cities.4 Ball et al tracked disruptions in acute cardiovascular services across nine UK hospitals.5 Taken together, these two studies quantify what many readers of this Journal have experienced firsthand. The restructuring of hospital services to cope with an influx of hypertension medications cases, combined with social distancing measures, has severely limited access to cardiovascular care, adversely impacting patient outcomes.Although Ball et al did not attempt to link reduced service delivery to mortality outcomes, other studies from the UK have estimated excess cardiovascular deaths during hypertension medications.5 Brant et al posited that excess cardiovascular mortality in Brazil was partly due to avoidance of care (ie, increases cardiovascular deaths occurring at home).4 They also found that healthcare system collapse in more socioeconomically deprived states was associated with increased acute coronary syndrome and stroke deaths in these states, independent of the uptick in deaths at home.A comprehensive responseWhat can be done about these disruptions?. The relationship between hypertension medications and cardiovascular health can be separated into two issues that require different responses.

First, persons living with cardiovascular diseases have worse outcomes when they acquire hypertension medications. On the other hand, persons living with cardiovascular disease or major risk factors are also at increased risk of death from cardiovascular mechanisms (eg, thrombotic events or heart failure) when their access to acute care services is interrupted. Health systems, patients and patient-system interactions are implicated in both of these issues.Figure 1 illustrates how an appropriate policy response should consider all of the elements mentioned above, with the overarching goal being to reduce deaths from any cause (hypertension medications or otherwise) among persons living with cardiovascular diseases or major risk factors. Importantly, the actions specified in the figure 1 can be adapted to all populations and countries, regardless of health system resource levels.

With such a framework in mind, practitioners and researchers could then structure their work and advocacy around two key messages.Message 1. The global and national lasix responses cannot be separated from the cardiovascular health agendaCritical elements of a comprehensive policy response to cardiovascular disease during hypertension medications. The elements proposed above can be modified to fit the resource levels and epidemiological contexts of different countries. Areas marked in red are those likely to translate into the largest short-term mortality gains.

Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality." data-icon-position data-hide-link-title="0">Figure 1 Critical elements of a comprehensive policy response to cardiovascular disease during hypertension medications. The elements proposed above can be modified to fit the resource levels and epidemiological contexts of different countries. Areas marked in red are those likely to translate into the largest short-term mortality gains. Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality.Outcomes from infectious diseases are usually worse among patients with multimorbidity, and hypertension medications is no different.

As cardiovascular practitioners, scientists and advocates, we need to articulate the substantial benefits of lasix mitigation efforts to persons living with cardiovascular diseases or risk factors. In parallel, accelerated investment in population-level prevention efforts would reduce the future burden of cardiovascular disease on health systems and reduce the number of persons at high risk of complications from future lasixs or outbreaks.In much of the global health community, investments in acute care and in cardiovascular diseases are often perceived to be non-essentialâor even anti-equityâand are almost never given serious consideration within health and development programmes. We need to forcefully push back on such short-sighted thinking. Collaborators on the Disease Control Priorities Project recently released guidance for low-income and middle-income and humanitarian settings, including a list of 120 essential health services to protect during the lasix.

On value-for-money grounds, basic cardiovascular disease prevention and care are just as âessentialâ as immunisation programmes, maternal healthcare and screening and treatment of HIV .6At the same time, locations with advanced cardiovascular care systems need guidance on how to balance the need to treat severe cardiovascular disease against the need to adapt quickly to increased hypertension medications caseloads. Ball et al found that emergency department visits and percutaneous coronary intervention procedure rates in UK hospitals had partially rebounded by the end of May 2020.5 Assuming the top objective is to maximise health, emergency cardiac care and interventional services should be brought back online before phasing in other semi-elective vascular procedures (even if the latter provide substantial revenues to hospitals). Critically, more must be done to encourage patients with acute cardiac or neurological symptoms to seek care even in the face of potential hypertension medications exposure. Initiatives like the American Heart Associationâs âDonât Die of Doubtâ campaign7 should be examined, adapted and disseminated widely to complement supply-side efforts to improve access.Message 2.

Cardiovascular research funders should prioritise development of truly âglobalâ public goods that can immediately benefit the health of the worldâs poorest as well as vulnerable populations in the global North.2How could the cardiovascular research community make this pivot?. Table 1 proposes several principles for cardiovascular research and development priorities amid and beyond the hypertension medications lasix. Not every concept in table 1 will be directly applicable to every research initiative, but they could be used by funders as benchmarks for developing or revising their strategies and scoring proposals.View this table:Table 1 Proposed principles to guide cardiovascular research and development prioritiesManagement of acute coronary syndromes exemplifies the need for a research and development pivot. Our ability to reduce case fatality from acute coronary syndromes is based on prompt delivery of interventions or fibrinolysis.

Researchers and planners have worked for years to improve referral and triage systems to increase access to these life-saving technologies. Yet when viewed through the lens of hypertension medications, it is problematic that the cornerstone of acute coronary syndrome management is early access to a referral hospital. We need new technologies, like home-based diagnostics and smartphone-based triage and referral processes, that can circumvent time and distance bottlenecks. We also need new drugs (available at home) that bridge to interventions or replace them entirely.

Such technologies are especially needed in low-income and middle-income countries, where systems are less advanced and timely access is more difficult to achieve (eg, in majority-rural countries).More generally, new technologies should âdisruptâ care systems in a way that makes cardiovascular care more patient-centred, community-facing and responsive to population needs. The notion that healthcare by default requires a physical building (separate from oneâs home or work) should quickly become antiquated. The greater use of telemedicine during the lasix is a big step in this direction, but we have yet to hardness the full potential of mobile devices and wearablesâtechnologies that are already widely available and will become ubiquitous in low-income and middle-income countries much more quickly than new clinics or hospitals. Innovators and health planners in resource-limited countries could collaborate to develop âleapfrogâ cardiovascular health programmes that do not rely on the inefficient, slow-to-adapt and labour-intensive models used in the global North.The future of cardiovascular health and researchIn the midst of the debate over the future of cardiovascular care, we should not to lose sight of the âendgameâ.8 In the long term, it would be far better to live in a world where the prevalence of ideal cardiovascular health is high and the lifetime disease risk is low.

In such a world, the impact of another lasix on cardiovascular services and patients would be lessened greatly. Aggressive action is needed to fully implement policies and health services that we know can help achieve this goal in a cost-effective manner. Still, in order to accomplish the endgame, we need better evidence on how to design policy instruments that can minimise dietary risks and barriers to optimal physical activityâthe most challenging of the risk factors to tackle.2hypertension medications has left an indelible mark on human health. At the end of 2019, many of us in the cardiovascular health community were probably quite comfortable with business as usual and with incremental improvements in science and clinical practice.

The events of 2020 have raised the stakes, forcing us to become more accepting of disruptions (creative or otherwise). We must use this opportunity to think more boldly..

The hypertension medications lasix continues to negatively impact population health by indirect effects on patient buy lasix tablets and healthcare systems, in addition to the direct effects of hypertension medications itself. Accurate and quantitative information about the indirect effects of the hypertension medications lasix on cardiovascular disease (CVD) services and outcomes will allow better public health planning. Ball and colleagues1 aim to âdesign and implement a simple tool for monitoring and visualising trends buy lasix tablets in CVD hospital services in the UKâ and towards that end they present pilot data from a preliminary cohort of nine UK hospitals in this issue of Heart. Comparing 6 months in 2019â2020 (that include the hypertension medications lockdown in the UK) to the same time period in 2018â2019, there was a 57.9% decrease in total hospital admissions and a 52.9% decrease in emergency department visits (figure 1). In addition, there was a 31%â88%âdecline during lockdown in procedures for treatment of cardiac, cerebrovascular and other vascular conditions.Overall hospital activity (admissions, ED attendances and hypertension medications admissions) between 31 October 2019 and 10 May 2020 compared with the same weeks from 2018 to 2019.

Lines describe the mean hospital activities in 2019â2020 buy lasix tablets (solid) and 2018â2019 (dotted). Shading represents 95%âCI of the respective hospital activity. The first case of hypertension medications was on 31 January 2020 and lockdown started on 23 March 2020. ED, emergency department." data-icon-position data-hide-link-title="0">Figure 1 Overall hospital activity buy lasix tablets (admissions, ED attendances and hypertension medications admissions) between 31 October 2019 and 10 May 2020 compared with the same weeks from 2018 to 2019. Lines describe the mean hospital activities in 2019â2020 (solid) and 2018â2019 (dotted).

Shading represents 95%âCI of the respective hospital activity. The first case of hypertension medications was on 31 January buy lasix tablets 2020 and lockdown started on 23 March 2020. ED, emergency department.From the other side of the world, Brant and colleagues2 report the number of cardiovascular deaths in the six Brazilian cities with the greatest number of hypertension medications deaths. They conclude. ÂExcess cardiovascular mortality was buy lasix tablets greater in the less developed cities, possibly associated with healthcare collapse.

Specified cardiovascular deaths decreased in the most developed cities, in parallel with an increase in unspecified cardiovascular and home deaths, presumably as a result of misdiagnosis. Conversely, specified cardiovascular deaths increased in cities with a healthcare collapseâ (figure 2).Per cent change with 95% CIs between the observed and expected number of deaths in 2020 for specified cardiovascular deaths (acute coronary syndromes and stroke) and unspecified cardiovascular diseases per selected six capital cities." data-icon-position data-hide-link-title="0">Figure 2 Per cent change with 95% CIs between the observed and expected number of deaths in 2020 for specified cardiovascular deaths (acute coronary syndromes and stroke) and unspecified cardiovascular diseases per selected six capital cities.In the accompanying editorial, Watkins3 notes that âTaken together, these two studies quantify what many readers of this journal have experienced firsthand. The restructuring of hospital services to cope with an influx of hypertension medications cases, combined with social distancing measures, has severely limited access to cardiovascular care, adversely impacting patient outcomes.â buy lasix tablets He then goes on to propose policy responses to reduce all-cause death among patients with CVD including deaths due to hypertension medications or to disruptions to healthcare delivery associated with the lasix (figure 3). His two key messages are. (1) âthe global and national lasix responses cannot be separated from the cardiovascular health agendaâ and (2) âpriorities for cardiovascular science must pivot, capitalising on lessons learnt during the lasixâ.Critical elements of a comprehensive policy response to cardiovascular disease during hypertension medications.

The elements proposed above can be modified to fit the resource levels and epidemiological contexts of different countries buy lasix tablets. Areas marked in red are those likely to translate into the largest short-term mortality gains. Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality." data-icon-position data-hide-link-title="0">Figure 3 Critical elements of a comprehensive policy response to cardiovascular disease during hypertension medications. The elements proposed above can be modified to fit the resource levels and buy lasix tablets epidemiological contexts of different countries. Areas marked in red are those likely to translate into the largest short-term mortality gains.

Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality.Other interesting papers in this issue of Heart include a study by Doris and colleagues4 showing that in adults with aortic stenosis CT quantitation of valve calcification is reproducible and demonstrates a greater rate of change in disease severity, compared with echocardiography. Guzzetti and Clavel5 point out that more precise measures of aortic stenosis (AS) severity will allow smaller sample sizes in clinical trials of potential medical therapies, in addition to providing insights into the pathophysiology of buy lasix tablets disease progression (figure 4).Model of AS progression. Pathophysiological model of serial AS progression (âaortic stenosis cascadeâ, in blue), along with imaging biomarkers targeting each phase (red) and potential disease-modifying treatments being currently tested in randomised clinical trials (green). 1South Korean PCSK9 inhibitors (NCT03051360). 2EAVaLL.

Early aortic valve lipoprotein(a) lowering (NCT02109614). 3SALTIRE II. Study investigating the effect of drugs used to treat osteoporosis on the progression of calcific aortic stenosis (NCT02132026). 4BASIK2. Bicuspid aortic valve stenosis and the effect of vitamin K2 on calcium metabolism on 18F-NaF PET/MRI (NCT02917525).

5EvoLVeD. Early valve replacement guided by biomarkers of left ventricular decompensation in asymptomatic patients with severe AS (NCT03094143). 6Early TAVR. Evaluation of transcatheter aortic valve replacement compared with surveillance for patients with asymptomatic severe aortic stenosis (NCT03042104). 18F-FDG, 18-fluorodeoxyglucose.

18F-NaF, 18-sodium fluoride. AS, aortic stenosis. AVC, aortic valve calcification. PET, positron emission tomography. PCSK9, proprotein convertase subtilisin/kexin type 9.

TAVR, transcatheter aortic valve replacement." data-icon-position data-hide-link-title="0">Figure 4 Model of AS progression. Pathophysiological model of serial AS progression (âaortic stenosis cascadeâ, in blue), along with imaging biomarkers targeting each phase (red) and potential disease-modifying treatments being currently tested in randomised clinical trials (green). 1South Korean PCSK9 inhibitors (NCT03051360). 2EAVaLL. Early aortic valve lipoprotein(a) lowering (NCT02109614).

3SALTIRE II. Study investigating the effect of drugs used to treat osteoporosis on the progression of calcific aortic stenosis (NCT02132026). 4BASIK2. Bicuspid aortic valve stenosis and the effect of vitamin K2 on calcium metabolism on 18F-NaF PET/MRI (NCT02917525). 5EvoLVeD.

AS, aortic stenosis. AVC, aortic valve calcification. PET, positron emission tomography. PCSK9, proprotein convertase subtilisin/kexin type 9. TAVR, transcatheter aortic valve replacement.In a study of patients undergoing atrial fibrillation (AF) ablation, Piccini and colleagues6 found that almost 30% experienced recurrent atrial tachycardiac (AT) or AF within 3 months.

However, although those without recurrent AT/AF had greater improvement in functional status, overall quality of life was similar in those with and without AT/AF recurrence. Sridhar and Colbert7 discuss the importance of patient-reported outcomes (PROs), not just âhardâ clinical endpoints in clinical trials. ÂAs researchers and clinicians, our goals must align with those of the patients and what they value. It is heartening to see that more and more clinical trials in cardiology and electrophysiology are incorporating PROs as important endpoints. A slow but definite paradigm shift is occurring to incorporate therapies with a focus on improving patientsâ lives, not just their hearts.âThe Education in Heart article in this issue discusses the diagnosis and management of familial hypercholesterolemia.8 Our Cardiology in Focus article âWhat to do when things go wrongâ provides a thoughtful discussion of the key steps in dealing with medical error.9 The Image Challenge in this issue10 provides a concise review of a sophisticated set of possible diagnoses to consider in a patient with a new murmur and classic echocardiographic images.

Be sure to look at our online Image Challenge archive with over 150 image-based multiple choice questions and answers (https://heart.bmj.com/pages/collections/image_challenges/).Global trends in cardiovascular health have reached a worrisome inflection point. Decades of innovation led to a slew of drugs, devices and programmes that translated into reduced mortality from cardiovascular diseases in many countries. Unfortunately, progress on cardiovascular mortality since 2010 has slowed. In some countries, it has even reversed.1 Compounding the problem, political actions on cardiovascular health have been inadequate, and health systems across many low-income and middle-income countries are woefully under-resourced to scale up basic cardiovascular services. These factors could increase global health inequalities in coming decades.2hypertension medications threatens to derail progress on cardiovascular health even furtherCardiovascular practitioners are now under greater pressure to deliver the same or better care in the context of a lasix.

hypertension medications has hit cardiovascular care particularly hard. WHO surveys recently found that cardiovascular services have been partially or completely disrupted in nearly half of countries with community spread of hypertension medications, raising the chance of increased cardiovascular mortality in these locations.3Two studies published in this issue of Heart shed more light on the specific effects of hypertension medications on health systems in Brazil and the UK. Brant et al looked at cardiovascular mortality in six Brazilian capital cities.4 Ball et al tracked disruptions in acute cardiovascular services across nine UK hospitals.5 Taken together, these two studies quantify what many readers of this Journal have experienced firsthand. The restructuring of hospital services to cope with an influx of hypertension medications cases, combined with social distancing measures, has severely limited access to cardiovascular care, adversely impacting patient outcomes.Although Ball et al did not attempt to link reduced service delivery to mortality outcomes, other studies from the UK have estimated excess cardiovascular deaths during hypertension medications.5 Brant et al posited that excess cardiovascular mortality in Brazil was partly due to avoidance of care (ie, increases cardiovascular deaths occurring at home).4 They also found that healthcare system collapse in more socioeconomically deprived states was associated with increased acute coronary syndrome and stroke deaths in these states, independent of the uptick in deaths at home.A comprehensive responseWhat can be done about these disruptions?. The relationship between hypertension medications and cardiovascular health can be separated into two issues that require different responses.

The global and national lasix responses cannot be separated from the cardiovascular health agendaCritical elements of a comprehensive policy response to cardiovascular disease during hypertension medications. The elements proposed above can be modified to fit the resource levels and epidemiological contexts of different countries. Areas marked in red are those likely to translate into the largest short-term mortality gains. Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality." data-icon-position data-hide-link-title="0">Figure 1 Critical elements of a comprehensive policy response to cardiovascular disease during hypertension medications. The elements proposed above can be modified to fit the resource levels and epidemiological contexts of different countries.

Areas marked in red are those likely to translate into the largest short-term mortality gains. Areas marked in yellow or green, while important for prevention, health promotion or stewardship objectives, are less likely to reduce mortality.Outcomes from infectious diseases are usually worse among patients with multimorbidity, and hypertension medications is no different. As cardiovascular practitioners, scientists and advocates, we need to articulate the substantial benefits of lasix mitigation efforts to persons living with cardiovascular diseases or risk factors. In parallel, accelerated investment in population-level prevention efforts would reduce the future burden of cardiovascular disease on health systems and reduce the number of persons at high risk of complications from future lasixs or outbreaks.In much of the global health community, investments in acute care and in cardiovascular diseases are often perceived to be non-essentialâor even anti-equityâand are almost never given serious consideration within health and development programmes. We need to forcefully push back on such short-sighted thinking.

Collaborators on the Disease Control Priorities Project recently released guidance for low-income and middle-income and humanitarian settings, including a list of 120 essential health services to protect during the lasix. On value-for-money grounds, basic cardiovascular disease prevention and care are just as âessentialâ as immunisation programmes, maternal healthcare and screening and treatment of HIV .6At the same time, locations with advanced cardiovascular care systems need guidance on how to balance the need to treat severe cardiovascular disease against the need to adapt quickly to increased hypertension medications caseloads. Ball et al found that emergency department visits and percutaneous coronary intervention procedure rates in UK hospitals had partially rebounded by the end of May 2020.5 Assuming the top objective is to maximise health, emergency cardiac care and interventional services should be brought back online before phasing in other semi-elective vascular procedures (even if the latter provide substantial revenues to hospitals). Critically, more must be done to encourage patients with acute cardiac or neurological symptoms to seek care even in the face of potential hypertension medications exposure. Initiatives like the American Heart Associationâs âDonât Die of Doubtâ campaign7 should be examined, adapted and disseminated widely to complement supply-side efforts to improve access.Message 2.

Priorities for cardiovascular science must pivot, capitalising on lessons learnt during the lasixIt is increasingly clear that lasixs and emerging s, driven by globalisation and climate change, will continue to threaten health systems in the coming decades. Cardiovascular research and development priorities must adapt to this emerging reality. We need new technologies, programmes and care systems that protect what is working during hypertension medications and transform what is not. In addition, the lasix has illuminatedâand in many cases magnifiedâinequalities in cardiovascular health. Cardiovascular research funders should prioritise development of truly âglobalâ public goods that can immediately benefit the health of the worldâs poorest as well as vulnerable populations in the global North.2How could the cardiovascular research community make this pivot?.

Table 1 proposes several principles for cardiovascular research and development priorities amid and beyond the hypertension medications lasix. Not every concept in table 1 will be directly applicable to every research initiative, but they could be used by funders as benchmarks for developing or revising their strategies and scoring proposals.View this table:Table 1 Proposed principles to guide cardiovascular research and development prioritiesManagement of acute coronary syndromes exemplifies the need for a research and development pivot. Our ability to reduce case fatality from acute coronary syndromes is based on prompt delivery of interventions or fibrinolysis. Researchers and planners have worked for years to improve referral and triage systems to increase access to these life-saving technologies. Yet when viewed through the lens of hypertension medications, it is problematic that the cornerstone of acute coronary syndrome management is early access to a referral hospital.

We need new technologies, like home-based diagnostics and smartphone-based triage and referral processes, that can circumvent time and distance bottlenecks. We also need new drugs (available at home) that bridge to interventions or replace them entirely. Such technologies are especially needed in low-income and middle-income countries, where systems are less advanced and timely access is more difficult to achieve (eg, in majority-rural countries).More generally, new technologies should âdisruptâ care systems in a way that makes cardiovascular care more patient-centred, community-facing and responsive to population needs. The notion that healthcare by default requires a physical building (separate from oneâs home or work) should quickly become antiquated. The greater use of telemedicine during the lasix is a big step in this direction, but we have yet to hardness the full potential of mobile devices and wearablesâtechnologies that are already widely available and will become ubiquitous in low-income and middle-income countries much more quickly than new clinics or hospitals.

Innovators and health planners in resource-limited countries could collaborate to develop âleapfrogâ cardiovascular health programmes that do not rely on the inefficient, slow-to-adapt and labour-intensive models used in the global North.The future of cardiovascular health and researchIn the midst of the debate over the future of cardiovascular care, we should not to lose sight of the âendgameâ.8 In the long term, it would be far better to live in a world where the prevalence of ideal cardiovascular health is high and the lifetime disease risk is low. In such a world, the impact of another lasix on cardiovascular services and patients would be lessened greatly. Aggressive action is needed to fully implement policies and health services that we know can help achieve this goal in a cost-effective manner. Still, in order to accomplish the endgame, we need better evidence on how to design policy instruments that can minimise dietary risks and barriers to optimal physical activityâthe most challenging of the risk factors to tackle.2hypertension medications has left an indelible mark on human health. At the end of 2019, many of us in the cardiovascular health community were probably quite comfortable with business as usual and with incremental improvements in science and clinical practice.

The events of 2020 have raised the stakes, forcing us to become more accepting of disruptions (creative or otherwise). We must use this opportunity to think more boldly..