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  • Benetos, Athanase; Petrovic, Mirko; Strandberg, Timo (2019)
    The prevalence of arterial hypertension, particularly systolic hypertension, is constantly rising worldwide. This is mainly the clinical expression of arterial stiffening as a result of the population's aging. Chronic elevation in blood pressure represents a major risk factor not only for cardiovascular morbidity and mortality but also for cognitive decline and loss of autonomy later in life. Clinical evidence obtained in community-dwelling older people with few comorbidities and preserved autonomy supports the beneficial effects of lowering blood pressure in older hypertensive subjects even after the age of 80 years. However, observational studies in frail older individuals treated for hypertension have shown higher morbidity and mortality rates compared with those with lower blood pressure levels. Clearly, in very old subjects, the therapeutic strategy of one size fits all cannot be applied because of the enormous functional heterogeneity in these individuals. Geriatric medicine proposes taking into account the function/ frailty/ autonomy status of older people. In the present review, we propose to adapt the antihypertensive treatment using an easy-to-apply visual numeric scale allowing the identification of 3 different patient profiles according to the functional status and autonomy for activities of daily living. For the preserved function profile, strategies should be those proposed for younger old adults. For the loss of function/ preserved activities of daily living' profile, a more detailed geriatric assessment is needed to define the benefit/ risk balance as well as requirements for the tailoring of the various therapeutic strategies. Lastly, for the loss of function and altered activities of daily living' profile, therapeutic strategies should be thoroughly reassessed, including deprescribing (when considered appropriate). In the near future, controlled trials are necessary for the most frail older subjects (ie, in those systematically excluded from previous clinical trials) to gain stronger evidence regarding the benefits of the various therapeutic strategies.
  • EuGMS Special Interest Grp; Alves, Mariana; Fernandes, Marilia Andreia; Bahat, Gülistan; Strandberg, Timo E. (2021)
    Purpose In the pathogenesis of severe COVID-19 complications, derangements of renin-angiotensin-aldosterone system (RAAS), vascular endothelial dysfunction leading to inflammation and coagulopathy, and arrhythmias play an important role. Therefore, it is worth considering the use of currently available drugs to protect COVID-19 patients with cardiovascular diseases. Methods We review the current experience of conventional cardiovascular drugs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, anticoagulants, acetosalicylic acid, antiarrhythmic drugs, statins] as well as some other drug classes (antidiabetic drugs, vitamin D and NSAIDs) frequently used by older patients with cardiovascular diseases. Data were sought from clinical databases for COVID-19 and appropriate key words. Conclusions and recommendations are based on a consensus among all authors. Results Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on retrospective, observational studies. Despite propensity score adjustments used in many analyses observational studies are not equivalent to randomised controlled trials (RCTs). Ongoing RCTs include treatment with antithrombotics, pulmonary vasodilators, RAAS-related drugs, and colchicine. RCTs in the acute phase of COVID-19 may not, however, recognise the benefits of long term anti-atherogenic therapies, such as statins. Conclusions Most current cardiovascular drugs can be safely continued during COVID-19. Some drug classes may even be protective. Age-specific data are scarce, though, and conditions which are common in older patients (frailty, comorbidities, polypharmacy) must be individually considered for each drug group. Key summary pointsAim To review current cardiovascular medications for benefits and potential harms during COVID-19. Findings Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on observational studies and age-specific data are scarce. Message Most current cardiovascular drugs can be safely continued during COVID-19, but general conditions common in older patients must be considered.
  • Salmenkari, Hanne; Korpela, Riitta; Vapaatalo, Heikki (2021)
    Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin-angiotensin system (RAS), besides being antihypertensive, also possess anti-inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS and the available evidence of the benefits of RAS inhibitors for IBD patients. Retrospective studies comparing IBD patients using ACE inhibitors or angiotensin II receptor blockers have provided optimistic results regarding a milder disease course and fewer hospitalizations and corticosteroid use in patients using RAS inhibitors. Prospective studies are needed to evaluate the effectiveness of these promising medications in the treatment of IBD.
  • Salmenkari, Hanne; Laitinen, Anita; Forsgård, Richard A.; Holappa, Mervi; Linden, Jere; Pasanen, Lauri; Korhonen, Matti; Korpela, Riitta; Nystedt, Johanna (2019)
    Background: Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various preclinical and clinical IBD studies is also challenging due to a large variation in study designs. Methods: In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryo-preserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1 beta and tumor necrosis factor (TNF)alpha concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1 beta and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis. Results: Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1 beta protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon. Conclusions: In conclusion, we observed a good safety profile for bone marrow-derived platelet lysate-expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.