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1.
Vasc Med ; : 1358863X19898262, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031495
2.
Am J Cardiol ; 125(1): 11-18, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732135

RESUMO

Although older adults are the fastest-growing age group among cardiovascular patients, nonagenarians with ST-segment elevation myocardial infarction (STEMI) are under-represented in clinical trials. The aims of this study are to analyze the clinical presentation and outcomes of nonagenarian patients presenting with STEMI and to compare in-hospital and 1-year clinical outcomes between those treated with optimal medical treatment alone and those receiving primary percutaneous coronary intervention (pPCI). We included all consecutive nonagenarians presenting with STEMI admitted in 2 academic centers between 2006 and 2018. There were no exclusion criteria. All-cause mortality was assessed in-hospital and at 1-year follow-up. In total, 167 patients (mean age 91.9 ± 0.17 years; 60% females) were included. Emergent catheterization was performed in 60% of our patients, and pPCI was performed in 50% (n = 83). Overall mortality was 22% in-hospital and 41% at 1-year follow-up. The pPCI group had lower mortality than the medical treatment group: 12% versus 32% in-hospital (p <0.01) and 26% versus 45% at 1-year follow-up (p <0.01), respectively. Multivariable analysis identified 4 independent predictors of all-cause mortality at 1 year: mechanical complications (adjusted odds ratio [OR] 9.25, p <0.01), Killip class III/IV (adjusted OR 4.22, p <0.01), serum creatinine at admission (mg/dl; adjusted OR 1.8, p <0.01), and pPCI (adjusted OR 0.52; p <0.05). In conclusion, STEMI in nonagenarians is becoming increasingly common. pPCI may be the preferred strategy in this high-risk cohort when a high grade of disability is not present. Hemodynamic compromise, the presence of complications related to myocardial infarction, renal impairment, and early revascularization may be related to prognosis in these patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31776847

RESUMO

Concurrent antiplatelet therapy (APT) is common during warfarin therapy but is less well-documented during direct oral anticoagulant (DOAC) therapy. Combined anticoagulant and APT use has been associated with increased bleeding risk without providing additional protection against thrombosis. This study aimed to describe single-center prescribing rates of DOAC + APT as well as compare bleeding rates between DOAC monotherapy and DOAC + APT cohorts. Patients receiving DOAC therapy were evaluated for APT use at the time of hospital discharge. Patients were categorized into DOAC monotherapy and DOAC + APT cohorts. Primary outcomes included DOAC + APT prescribing rate as well as rates of major bleeding and clinically relevant non-major bleeding (CRNMB) within six months after hospital discharge. Secondary outcomes included rates of thromboembolism and all-cause mortality. Of 407 patients receiving DOAC therapy, 78 (19.2%) also received APT at hospital discharge. Common indications for APT included secondary cardiovascular event prevention (57.7%) and primary cardiovascular event prevention (29.5%). The indication for APT could not be determined in 12.8% of patients. The major bleeding rate was 1.3% for DOAC + APT and 1.2% for DOAC monotherapy (p = 0.95). The CRNMB rate was 10.2% for DOAC + APT and 6.4% for DOAC monotherapy (p = 0.23). Thromboembolism and mortality were infrequent in both cohorts. DOAC + APT was documented in approximately 1 of 5 patients. Adding APT to DOAC therapy did not significantly increase the major bleeding or CRNMB rates compared to DOAC monotherapy but the sample size limits drawing conclusions about the safety of these regimens. Targeting primary prevention or unclear indications for APT could be a focus of future interventions.

4.
Thromb Res ; 183: 4-12, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505378

RESUMO

INTRODUCTION: Warfarin dosing algorithms have proven beneficial in increasing time within therapeutic range (TTR) and decreasing adverse events associated with out-of-range international normalized ratios (INRs). Despite widespread availability, providers' utilization and perceptions of warfarin algorithms in real-world practice are unclear. Identifying perceptions and barriers to algorithm use may help attempts to improve warfarin therapy management. METHODS: Anticoagulation providers' utilization and perceptions of warfarin dosing algorithms were assessed via a nationwide electronic survey. RESULTS: Of the 246 providers who completed the survey, 82% were pharmacists, and 69% had over five years' experience dosing warfarin. Warfarin dosing algorithms were deemed beneficial by 84% of respondents and 72% currently use a warfarin dosing algorithm in their practice at least occasionally. Pharmacists were least likely of anticoagulation providers to use algorithms, although this was not statistically significant (p = 0.12). Algorithm utilization also decreased as years of warfarin dosing experience increased, with the highest rate of usage noted in the first year of dosing warfarin. The most common reason providers gave for discontinuing algorithm use was that they no longer felt it was needed. In this study, clinic patient volume did not appear to be associated with algorithm utilization. CONCLUSION: Warfarin dosing algorithms are frequently used among anticoagulation providers, especially those new to dosing warfarin, but use is frequently not sustained over the long-term. Education on the continued benefits of warfarin dosing algorithms could increase long-term utilization, potentially improving patient outcomes.

5.
Exp Eye Res ; 187: 107751, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394104

RESUMO

The vascular endothelium responds to the shear stress generated by blood flow and changes function to maintain tissue homeostasis and adapt to injury in pathological conditions. Shear stress in the retinal circulation is altered in patients with retinal vascular diseases, such as diabetic retinopathy. Therefore, we aimed to study the effect of laminar shear stress on barrier properties and on the release of proinflammatory cytokines in human retinal microvascular endothelial cells (HRMEC). HRMEC were cultured in Ibidi flow chambers and exposed to laminar shear stress (0-50 dyn/cm2) for 24-48 h. Tight junction distribution (ZO-1 and claudin-5) and cytokine production were determined by immunofluorescence and ELISA, respectively. The chemotactic effect of conditioned media exposed to shear stress was determined by measuring lymphocyte transmigration in Transwells. We found that cells exposed to moderately low shear stress (1.5 and 5 dyn/cm2) showed enhanced distribution of membrane ZO-1 and claudin-5 and decreased production of the proinflammatory cytokines IL-8, CCL2, and IL-6 compared to static conditions and high shear stress values. Moreover, conditioned media from cells exposed to low shear stress, had the lowest chemotactic effect to recruit lymphocytes compared to conditioned media from cells exposed to static and high shear stress conditions. In conclusion, high shear stress and static flow, associated to impaired retinal circulation, may compromise the inner blood retinal barrier phenotype and barrier function in HRMEC.

6.
J Thromb Thrombolysis ; 48(4): 623-628, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31317300

RESUMO

Certain patient populations (pregnancy, cancer, renal impairment, and obesity) may be at higher risk of adverse events during low molecular weight heparin (LMWH) therapy and may benefit from anti-Xa monitoring. Yet, evidence supporting a standardized approach to anti-Xa monitoring correlated to clinical outcomes is lacking. Patients with at least one documented anti-Xa level and receiving LMWH within a 6-month period were identified. In a 6-month period, 224 adult LMWH patients with 359 anti-Xa levels were identified. Anti-Xa monitoring was most commonly performed in patients with active cancer receiving venous thromboembolism (VTE) treatment doses (57.4%) or obese patients receiving VTE prophylaxis (48.1%). Anti-Xa monitoring during renal impairment and pregnancy were infrequent (0.9% and 1.8%, respectively). Most (71.9%) anti-Xa levels were therapeutic, but only 45% were drawn correctly in relation to LMWH administration time. Compared to those with therapeutic anti-Xa levels, patients with out-of-range levels were four times as likely to receive a LMWH therapy change (odds ratio, 4.16; 95% confidence interval, 2.53-6.84). However, when levels were supratherapeutic or subtherapeutic, the LMWH doses remained unchanged in one-third to one-half of patients, respectively. Anti-Xa monitoring was most commonly performed in patients with cancer or obesity and was more common with VTE prophylaxis dosing. The majority of levels were therapeutic, indicating that anti-Xa monitoring may be unnecessary even in high-risk patient populations. Many out-of-range anti-Xa levels did not prompt a change in LMWH therapy. Further research is still needed to determine if anti-Xa- guided LMWH dosing improves clinical outcomes.

7.
J Thromb Thrombolysis ; 48(4): 596-602, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31273515

RESUMO

Warfarin remains the most commonly prescribed oral anticoagulant in the United States, but it has disadvantages such as dietary interactions and frequent laboratory monitoring. Direct oral anticoagulants (DOACs) have been introduced as safer and equally effective alternatives to warfarin. This study assessed patient preference for warfarin or DOAC based on a willingness to pay more for potential DOAC benefits. Current warfarin patients with atrial fibrillation or venous thromboembolism enrolled in the University of Utah Health Thrombosis Service were given a one-time electronic survey that assessed preferences between warfarin and DOACs using scenarios comparing effectiveness, safety, and convenience. When DOACs were preferred, patients were asked how much more they would be willing to pay monthly for the perceived advantages associated with DOACs. With 123 completed surveys, 68% of patients preferred to stay on warfarin. No particular factor influenced patient preference (lack of routine laboratory monitoring, lower risks of major bleeding, and fewer dietary interactions). Reduced stroke risk was associated with the highest value (willing to pay an additional $21). Considering all factors, patients preferring DOACs would pay a median $18 extra per month for the additional benefits. Prior exposure to DOACs was associated with preference for DOACs. Many patients currently taking warfarin preferred to stay on warfarin when given the choice, despite DOAC benefits. Willingness to pay extra for DOAC advantages did not exceed $20 in the majority of survey respondents. Previous DOAC exposure influences patient preference and perceived value for DOACs.

8.
N Engl J Med ; 381(1): 47-54, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269365

RESUMO

A 37-year-old man with a history of seminoma presented with vertigo, ataxia, and diplopia. An autoantibody specific for kelch-like protein 11 (KLHL11) was identified with the use of programmable phage display. Immunoassays were used to identify KLHL11 IgG in 12 other men with similar neurologic features and testicular disease. Immunostaining of the patient's IgG on mouse brain tissue showed sparse but distinctive points of staining in multiple brain regions, with enrichment in perivascular and perimeningeal tissues. The onset of the neurologic syndrome preceded the diagnosis of seminoma in 9 of the 13 patients. An age-adjusted estimate of the prevalence of autoimmune KLHL11 encephalitis in Olmsted County, Minnesota, was 2.79 cases per 100,000 men. (Funded by the Rochester Epidemiology Project and others.).


Assuntos
Autoanticorpos/análise , Encéfalo/imunologia , Proteínas de Transporte/imunologia , Técnicas de Visualização da Superfície Celular , Encefalite/imunologia , Doença de Hashimoto/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Seminoma/complicações , Neoplasias Testiculares/complicações , Adulto , Idoso , Encefalite/epidemiologia , Doença de Hashimoto/epidemiologia , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência
10.
J Thromb Thrombolysis ; 48(3): 506-510, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31230262

RESUMO

Preferred anticoagulation therapy for venous thromboembolism (VTE) has shifted from warfarin to direct oral anticoagulants (DOACs). Adherence to DOAC prescribing information is an important quality measure as off-label doses have been associated with increased risk of adverse events (AEs). To identify the prevalence, outcomes, and patient characteristics associated with off-label DOAC dosing during VTE treatment. Patients receiving DOAC for VTE treatment discharged from University of Utah Health (UUH) over a 90-day period were identified. Dosing was classified as "labeled" or "off-label" based on concordance with manufacturer prescribing information. AEs (thromboembolic events, bleeding, death) occurring within 90 days after discharge were identified. Out of 195 patients, 154 (79.0%) received labeled dosing, 31 (15.9%) received off-label dosing, and 10 (5.1%) were indeterminate. Two-thirds of off-label doses were higher than recommended and three-fourths occurred during extended treatment (more than 90 days post-VTE). Off-label dosing rates dropped to 5.6% when 6-month dose reductions were not required. Off-label dosing was associated with apixaban use and extended phase treatment (p < 0.001). No association was found between off-label dosing and age, renal function, prescriber rationale for dose selection, or Thrombosis Clinic referral. AEs were experienced by 18 (11.7%) and 3 (9.7%) patients in the labeled and off-label groups, respectively (p = 0.77). Bleeding events comprised 46.2% of AEs. The rate of off-label DOAC dosing for VTE at UUH was within rates reported in prior studies, occurred primarily with extended-duration apixaban, and did not result in a higher rate of AEs.

12.
Catheter Cardiovasc Interv ; 94(4): 527-535, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30828975

RESUMO

BACKGROUND: Chronic total occlusions (CTOs) are present in more than one third of older patients with myocardial ischemia, but controversy remains about the best therapeutic approach. AIMS: To compare long-term survival after CTO revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) versus medical treatment (MT) alone in patients aged 75 and older. METHODS AND RESULTS: A total of 1,252 consecutive patients with at least one CTO were identified from 2010 to 2014 in our center. Patients were stratified by age (<75 years vs. ≥75 years) in the present analysis. All-cause and cardiac mortality were assessed at a median follow-up of 3.5 years. In the older subgroup (26%), patients were more likely to be treated with MT alone (71% vs. 43% of younger patients; p < 0.001). Patients undergoing revascularization were younger and had higher left ventricular ejection fraction (LVEF) and lower age, creatinine, ejection fraction (ACEF) score (age/LVEF +1 if creatinine >2.0 mg/dL), compared to the MT group (p < 0.05). As compared to MT, revascularization predicted lower rates of cardiac mortality and all-cause mortality in older patients, both in the subgroups treated with CABG (hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.17-0.71; HR 0.39, 95%CI 0.18-0.81) and PCI (HR 0.57, 95%CI 0.33-0.98; HR 0.59, 95%CI 0.28-1.2). No differences in mortality were observed according to type of revascularization procedure. CONCLUSIONS: Among patients aged at least 75 years with a CTO, revascularization (PCI or CABG) rather than MT alone may portend a better outcome in terms of all-cause and cardiac mortality.

13.
Fam Pract ; 36(5): 627-633, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30772892

RESUMO

BACKGROUND: The efficacy of smoking cessation interventions can be quite diverse in day-to-day clinical practice. OBJECTIVE: To analyse the effectiveness in smoking cessation of multicomponent interventions carried out in groups or individually in primary care practices. METHODS: A quasi-experimental, multicentre study of 12-month follow-up of patients treated in multicomponent smoking cessation interventions was carried out in Urban health care centres in Sevilla, Spain. Two hundred and twenty smoking patients, ≥18 years of age, participated either in a multicomponent intervention group (n = 145; mean age 51.7 years; 53.1% women) or in individual interventions (n = 77; mean age 50.5 years; 61.0% women). The abstinence or relapse status was computed from patient self-reports, confirmed by relatives or companions when possible and supplemented by CO-oxymetry tests in 89 patients. RESULTS: The overall percentage of smoking cessation was 36.9% (37.9% with group and 35.1% with individual intervention, P = 0.398). Patients who quit smoking were younger (48.7 versus 52.9 years old, P < 0.01), with fewer years of smoking (32.9 versus 36.8 years, P < 0.05), with higher education (39.0% versus 25.0%, P < 0.05) and had received pharmacological treatment (91.5% versus 67.9%, P < 0.001). In the multivariate analysis, level of education [odds ratio (OR): 1.995; 95% confidence interval (CI): 1.065-3.735, P < 0.01], group intervention (OR: 1.743; 95% CI: 1.006-3.287, P < 0.05) and drug prescription (OR: 2.368; 95% CI: 1.126-4.980, P < 0.05) were significantly associated with smoking cessation. CONCLUSIONS: Our study found that multicomponent group and individual interventions in primary care were associated with an overall quit rate of smoking of 36.9% at 12-month follow-up, with higher probability of success among patients with higher education and those who received the group intervention and drug treatment.

15.
Hematology Am Soc Hematol Educ Program ; 2018(1): 339-347, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504330

RESUMO

Oral anticoagulants are commonly prescribed but high risk to cause adverse events. Skilled drug interaction management is essential to ensure safe and effective use of these therapies. Clinically relevant interactions with warfarin include drugs that modify cytochrome 2C9, 3A4, or both. Drugs that modify p-glycoprotein may interact with all direct oral anticoagulants, and modifiers of cytochrome 3A4 may interact with rivaroxaban and apixaban. Antiplatelet agents, nonsteroidal anti-inflammatory drugs, and serotonergic agents, such as selective serotonin reuptake inhibitors, can increase risk of bleeding when combined with any oral anticoagulant, and concomitant use should be routinely assessed. New data on anticoagulant drug interactions are available almost daily, and therefore, it is vital that clinicians regularly search interaction databases and the literature for updated management strategies. Skilled drug interaction management will improve outcomes and prevent adverse events in patients taking oral anticoagulants.


Assuntos
Anti-Inflamatórios não Esteroides , Anticoagulantes , Inibidores da Agregação de Plaquetas , Inibidores de Captação de Serotonina , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP3A/metabolismo , Interações de Medicamentos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico
16.
Blood ; 132(21): 2230-2239, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30463993

RESUMO

Oral anticoagulants are commonly prescribed but high risk to cause adverse events. Skilled drug interaction management is essential to ensure safe and effective use of these therapies. Clinically relevant interactions with warfarin include drugs that modify cytochrome 2C9, 3A4, or both. Drugs that modify p-glycoprotein may interact with all direct oral anticoagulants, and modifiers of cytochrome 3A4 may interact with rivaroxaban and apixaban. Antiplatelet agents, nonsteroidal anti-inflammatory drugs, and serotonergic agents, such as selective serotonin reuptake inhibitors, can increase risk of bleeding when combined with any oral anticoagulant, and concomitant use should be routinely assessed. New data on anticoagulant drug interactions are available almost daily, and therefore, it is vital that clinicians regularly search interaction databases and the literature for updated management strategies. Skilled drug interaction management will improve outcomes and prevent adverse events in patients taking oral anticoagulants.


Assuntos
Anticoagulantes/farmacologia , Interações de Medicamentos , Varfarina/farmacologia , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/metabolismo , Indutores do Citocromo P-450 CYP2C9/farmacologia , Indutores do Citocromo P-450 CYP3A/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Varfarina/administração & dosagem , Varfarina/metabolismo
17.
Blood Adv ; 2(22): 3317-3359, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482767

RESUMO

BACKGROUND: Venous thromboembolism (VTE) complicates ∼1.2 of every 1000 deliveries. Despite these low absolute risks, pregnancy-associated VTE is a leading cause of maternal morbidity and mortality. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and others in decisions about the prevention and management of pregnancy-associated VTE. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS: The panel agreed on 31 recommendations related to the treatment of VTE and superficial vein thrombosis, diagnosis of VTE, and thrombosis prophylaxis. CONCLUSIONS: There was a strong recommendation for low-molecular-weight heparin (LWMH) over unfractionated heparin for acute VTE. Most recommendations were conditional, including those for either twice-per-day or once-per-day LMWH dosing for the treatment of acute VTE and initial outpatient therapy over hospital admission with low-risk acute VTE, as well as against routine anti-factor Xa (FXa) monitoring to guide dosing with LMWH for VTE treatment. There was a strong recommendation (low certainty in evidence) for antepartum anticoagulant prophylaxis with a history of unprovoked or hormonally associated VTE and a conditional recommendation against antepartum anticoagulant prophylaxis with prior VTE associated with a resolved nonhormonal provoking risk factor.


Assuntos
Anticoagulantes/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Aleitamento Materno , Medicina Baseada em Evidências , Feminino , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Lactente , Recém-Nascido , Gravidez , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevenção & controle
18.
Rev Port Cardiol ; 37(10): 865.e1-865.e4, 2018 10.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30355462

RESUMO

INTRODUCTION: Chronic total occlusion (CTO) of the left main coronary artery (LMCA) is an infrequent finding. Revascularization is recommended in the presence of demonstrated viability or ischemia. Coronary artery bypass grafting (CABG) has long been considered the preferred option. Patients with previous CABG due to LMCA disease with occlusion of one graft and progression of the LMCA to CTO constitute a special population, as just one ischemic artery remains. For these patients, there is no other option for revascularization other than cardiac surgery (requiring resternotomy) or percutaneous coronary intervention (PCI) of the LMCA. METHODS AND RESULTS: Out of 620 patients with CTO diagnosed in our center, we identified five with previous CABG due to LMCA disease for a retrospective case series. They had occlusion of one graft and progression of the LMCA to CTO. All five underwent PCI. Each patient received a functional classification for angina, myocardial ischemic tests, and a follow-up coronary angiogram during a median follow-up of 63 months. Coronary angiogram showed CTO of the semi-protected LMCA lesions with two CABGs previously performed in all patients, one occluded and the other patent. Three patients had occluded saphenous vein grafts to the circumflex coronary artery, and the rest had left internal mammary artery-left anterior descending artery CABG failure. Ischemia and viability were demonstrated. Surgery was ruled out due to high surgical risk. PCI due to CTO of the LMCA with drug-eluting stents was performed. In a five-year follow-up period, four patients remained asymptomatic and event free. One post-PCI death occurred from non-cardiovascular cause. CONCLUSIONS: PCI due to CTO of the LMCA following CABG can be successful and safe and can provide sustained clinical improvements in selected cases.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana , Intervenção Coronária Percutânea/métodos , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Front Immunol ; 9: 808, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29725335

RESUMO

Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro. In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.


Assuntos
Proteína C-Reativa/imunologia , Degeneração Macular/fisiopatologia , Idoso , Proteínas do Sistema Complemento , Progressão da Doença , Humanos , Inflamação , Degeneração Macular/genética , Terapia de Alvo Molecular , Estresse Oxidativo , Drusas Retinianas/genética , Drusas Retinianas/patologia , Epitélio Pigmentado da Retina/patologia , Fatores de Risco
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