36-month clinical outcomes of patients with venous thromboembolism: GARFIELD-VTE.

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population.

Diagnostic role of new Doppler index in assessment of renal artery stenosis.

BACKGROUND: Renal artery stenosis (RAS) is one of the main causes of secondary systemic arterial hypertension. Several non-invasive diagnostic methods for RAS have been used in hypertensive patients, such as color Doppler ultrasound (US). The aim of this study was to assess the sensitivity and specificity of a new renal Doppler US direct-method parameter: the renal-renal ratio (RRR), and compare with the sensitivity and specificity of direct-method conventional parameters: renal peak systolic velocity (RPSV) and renal aortic ratio (RAR), for the diagnosis of severe RAS. METHODS: Our study group included 34 patients with severe arterial hypertension (21 males and 13 females), mean age 54 (+/- 8.92) years old consecutively evaluated by renal color Doppler ultrasound (US) for significant RAS diagnosis. All of them underwent digital subtraction arteriography (DSA). RAS was significant if a diameter reduction > 50% was found. The parameters measured were: RPSV, RAR and RRR. The RRR was defined as the ratio between RPSV at the proximal or mid segment of the renal artery and RPSV measured at the distal segment of the renal artery. The sensitivity and specificity cutoff for the new RRR was calculated and compared with the sensitivity and specificity of RPSV and RAR. RESULTS: The accuracy of the direct method parameters for significant RAS were: RPSV >200 cm/s with 97% sensitivity, 72% specificity, 81% positive predictive value and 95% negative predictive value; RAR >3 with 77% sensitivity, 90% specificity, 90% positive predictive value and 76% negative predictive value. The optimal sensitivity and specificity cutoff for the new RRR was >2.7 with 97% sensitivity (p < 0.004) and 96% specificity (p < 0.02), with 97% positive predictive value and 97% negative predictive value. CONCLUSION: The new RRR has improved specificity compared with the direct method conventional parameters (RPSV >200cm/s and RAR >3). Both RRR and RPSV show better sensitivity than RAR for the RAS diagnosis.

Efficacy assessment of meloxicam, a preferential cyclooxygenase-2 inhibitor, in acute coronary syndromes without ST-segment elevation: the Nonsteroidal Anti-Inflammatory Drugs in Unstable Angina Treatment-2 (NUT-2) pilot study.

BACKGROUND: Despite the use of heparin, aspirin, and other antiplatelet agents, acute coronary syndrome patients without ST-segment elevation remain at risk of cardiovascular thrombotic events. Given the role of inflammation in the pathogenesis of arterial thrombosis, we tested the hypothesis that the combination of meloxicam, a preferential COX-2 inhibitor, and heparin and aspirin would be superior to heparin and aspirin alone. METHODS AND RESULTS: In an open-label, randomized, prospective, single-blind pilot study, patients with acute coronary syndromes without ST-segment elevation were randomized to aspirin and heparin treatment (n=60) or aspirin, heparin, and meloxicam (n=60) during coronary care unit stay. Patients then received aspirin or aspirin plus meloxicam for 30 days. During the coronary care unit stay, the primary outcomes variable of recurrent angina, myocardial infarction, or death was significantly lower in the patients receiving meloxicam (15.0% versus 38.3%, P=0.007). The second composite variable (coronary revascularization procedures, myocardial infarction, and death) was also significantly lower in meloxicam-treated patients (10.0% versus 26.7%, P=0.034). At 90 days, the primary end point remained significantly lower in the meloxicam group (21.7% versus 48.3%, P=0.004), as did the secondary end point (13.3% versus 33.3%, P=0.015) and the need for revascularization alone (11.7% versus 30.0%, P=0.025). No adverse complications associated with the meloxicam treatment were observed. CONCLUSIONS: Meloxicam with heparin and aspirin was associated with significant reductions in adverse outcomes in acute coronary syndrome patients without ST-segment elevation. Additional larger trials are required to confirm the findings of this pilot study.

SCA con elevación del ST: impacto del tiempo al diagnóstico en el tiempo puerta-balón en el mundo real. Datos del registro ARGEN-IAM-ST / ST-Segment Elevation ACS: Impact of Time to Diagnosis on Door-To-Balloon Time in the Real World. Data from the ARGEN-IAM-ST Registry

RESUMEN • Introducción: El tiempo trascurrido desde el inicio de los síntomas de infarto hasta el diagnóstico (TAD) puede influir en lograr un tiempo puerta-balón (TPB) <90 min. Material y métodos: Análisis retrospectivo que incluyó 1518 pacientes ingresados en forma prospectiva y consecutiva al registro ARGEN-IAM-ST. El 37,8% de ellos fue tratado con un TPB <90 min y el TAD (mediana) fue de 120 min (RIC 60-266). Se dividió a la población de acuerdo al TAD en dos grupos: menor de 120 min y mayor o igual que 120 min. Un TPB <90 min se logró más frecuentemente en el primer grupo (TAD <120 min): 44%, vs. 32,2% en el segundo grupo (p <0,001). Resutados: En el 56% de los pacientes con ATC in situ y TAD <120 min se logró un TPB <90 min, vs. en el 37,1% de quienes tuvieron un TAD >120 min (p <0,001). En pacientes derivados, no hubo diferencias en TPB <90 min de acuerdo al TAD: 27,5% vs. 25,7 (p: 0,3). En pacientes ingresados en horario laborable, el TPB <90 min se logró con TAD <120 min en un 49,8% vs. 36,3% con TAD >120 min (p: 0,003); la frecuencia siguió un patrón similar en los pacientes ingresados en horarios no laborables: 41,9% vs. 30,4%, respectivamente (p <0,001). Los predictores independientes de lograr un TPB <90 min en el análisis multivariado fueron la edad <75 años: OR 1,57 (1,1-2,25; p: 0,01), ATC en horario laborable: OR 1,32 (1,04-1,67; p: 0,002), ATC in situ: OR 2,4 (1,9-3,0; p <0,001), tener un ECG prehospitalario: OR 2,22 (1,73-2,86; p <0,001) y un TAD <120 min: OR 1,53 (1,23-1,9; p <0,001). Conclusiones: En los pacientes con un TAD <120 minutos se logra más frecuentemente un TPB <90 min, especialmente en los tratados in situ y en horario laborable. En los pacientes derivados, solo 1 de cada 3 logra un TPB <90 min y no hay relación con el TAD.

ABSTRACT • Background: Time elapsed from the onset of symptoms to diagnosis (TTD) can influence in achieving a door-to-balloon time <90 min (DBT <90 min). Methods: A retrospective analysis was performed on 1,518 patients prospectively and consecutively included in the ARGEN-AMI-ST registry. In 37.8% of cases. patients were treated with DBT <90 min and a median TTD of 120 min (IQR 60-266). The population was divided according to TTD above or below 120 min. A DBT <90 min was achieved more frequently in those with TTD <120 min: 44% vs. 32.2% (p <0.001) respectively. Results: In patients with in situ percutaneous coronary intervention (PCI) and TTD <120 min, DBT <90 min was achieved in 56% vs. 37.1% of cases with TTD >120 min (p <0.001). In referred patients, there were no differences in DBT <90 min according to TTD: 27.5% vs. 25.7% (p: 0.3). In patients admitted during working hours, DBT <90 min was achieved with TTD <120 min in 49.8% vs. 36.3% with TTD >120 min (p: 0.003), as well as in patients admitted during non-working hours: 41.9% vs. 30.4% (p <0.001). The independent predictors of achieving a DBT <90 min in the multivariate analysis were age <75 years: OR 1.57 (1.1-2.25; p: 0.01), PCI during working hours: OR 1.32 (1.04-1.67; p: 0.002), PCI in situ: OR 2.4 (1.9-3.0; p <0.001), having a pre-hospital ECG: OR 2.22 (1.73-2.86; p <0.001) and a TTD <120 min: OR 1.53 (1.23-1.9; p <0.001). Conclusions: In patients with TTD <120 minutes, a DBT <90 minutes is more frequently achieved, especially in those treated in situ and during working hours. In referred patients, only 1 in 3 achieves a DBT<90 min and there is no relationship with TTD.

Facilitated thrombolysis: dethrombosis?

Intracoronary thrombus formation results from the combined effects of platelet aggregation and fibrin formation. Fibrinogen plays a significant role in each of these components. Dethrombosis is a therapeutic approach that allows dissolution of a recent thrombus while avoiding the potent fibrinolytic therapies. The less aggressive strategies suggested to achieve dethrombosis are antifibrin, antiplatelet, and defibrinogenation. Glycoprotein receptor antagonists have been beneficial in patients undergoing percutaneous transluminal coronary angioplasty; however, little is known about their potency of inducing reperfusion in acute myocardial infarction. Early use of the strategies suggested to induce dethrombosis (antifibrin, antiplatelet, and defibrinogenation) may facilitate fibrinolysis and primary angioplasty and further induce reperfusion. Nevertheless, the theoretical arguments of facilitated thrombolysis (dethrombosis) have not yet been fruitful as a major clinical benefit except in patients undergoing primary percutaneous coronary intervention.

[The prothrombotic state in early stages of chronic chagas' disease]. / Estado protrombótico en estadios tempranos de la enfermedad de Chagas crónica.

OBJECTIVE: This study was designed to explore the presence of a prothrombotic state in the early stages of chronic Chagas' disease by evaluating serum markers of thrombosis and fibrinolysis. PATIENTS AND METHOD: Forty-two patients with chronic Chagas' disease (12 men and 30 women, 32.5 6.7 years) were compared with 21 healthy volunteers (10 men and 11 women, 24.2 5.6 years). The markers of thrombotic activation used were fragment 1 + 2, ATM complex, PDF/pdf, D-dimer, and beta-thromboglobulin. Fibrinolysis was evaluated before and after venous occlusion, together with euglobulin lysis time, t-PA, and PAI-1 titers. RESULTS: The markers of thrombotic state were significantly higher in patients with chronic Chagas' disease than in controls: F1 + 2 (p < 0.0001), ATM (p < 0.0001), PDF/pdf (p < 0.05), and D dimer (p < 0.05). There was no significant difference in beta-thromboglobulin (p = 0.06). Euglobulin lysis time, a global fibrinolytic marker, differed significantly (p < 0.0001) between patients with Chagas' disease and healthy volunteers. However, the more specific fibrinolytic markers t-PA and PAI-1 did not differ significantly between the two study groups. CONCLUSIONS: Although there were no significant differences in fibrinolytic markers between patients with chronic Chagas' disease and healthy volunteers, the significant increase in thrombosis markers (F1 + 2, ATM complex, PDF/pdf, and D dimer) suggests the presence of a prothrombotic state in the early stages of chronic Chagas' disease.

[Determination of blood markers and inflammation in subjects with impaired glucose tolerance]. / Determinación de marcadores séricos de trombosis e inflamación en sujetos con intolerancia a la glucosa: evidencia de un estado protrombótico.

OBJECTIVE: This study was designed to explore the presence of a prothrombotic state, fibrinolytic dysfunction and inflammation in impaired glucose tolerance subjects, by evaluating serum markers of thrombosis, fibrinolysis and inflammation. METHODS: In 48 consecutive adults, 25 patients with impaired glucose tolerance (nine men and 16 women, 50.0 ± 9.2 years) were compared with 23 control subjects (six men and 17 women, 48.0 ± 11 years). The markers of thrombotic activation used were D-dimer and fibrinogen. Fibrinolysis dysfunction was evaluated with plasminogen activator inhibitor 1 (PAI-1) and the inflammatory marker studied was hs-C reactive protein (hs-CRP). RESULTS: The markers of thrombotic state were significantly higher in patients with impaired glucose tolerance (IGT) than in controls: D dimer (489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL) (p< 0.01) and fibrinogen (317.7 ± 32.1 vs. 266.7 ± 25.4 mg/dL) (p < 0.0001). Fibrinolytic marker PAI-1 also differed significantly between the two study groups (66.4 ± 30.7 vs. 35.5 ± 31.0 ng/mL) (p < 0.006). However, hs-CRP, as inflammation marker, (0.45 ± 0.62 mg/dL vs. 0.38 ± 0.47) did not differ significantly between the two study groups (<0.28). CONCLUSION: This result suggests the presence of a prothrombotic state with fibrinolytic dysfunction in subjects with impaired glucose tolerance.

Oxidative stress in hypertensive patients induces an increased contractility in vein grafts independent of endothelial function.

Objective. To evaluate the impact of oxidative stress on vascular reactivity to vasoconstrictors and on nitric oxide (NO) bioavailability in saphenous vein (SV) graft with endothelial dysfunction from hypertensive patients (HT). Methods. Endothelial function, vascular reactivity, oxidative state, nitrites and NO release were studied in isolated SV rings from HT and normotensive patients (NT). Only rings with endothelial dysfunction were used. Results. HT rings presented a hyperreactivity to vasoconstrictors that was reverted by diphenylene iodonium (DPI). In NT, no effect of DPI was obtained, but Nω-nitro-(L)-arginine methyl ester (L-NAME) increased the contractile response. NO was present in SV rings without endothelial function. Nitrites were higher in NT than in HT (1066.1 ± 86.3 pmol/mg; n = 11 versus 487.8 ± 51.6; n = 23; P < 0.01) and inhibited by nNOS inhibitor. L-arginine reversed this effect. Antioxidant agents increased nitrites and NO contents only in HT. The anti-nNOS-stained area by immunohistochemistry was higher in NT than HT. HT showed an elevation of oxidative state. Conclusions. Extraendothelial NO counter-regulates contractility in SV. However, this action could be altered in hypertensive situations by an increased oxidative stress or a decreased ability of nNOS to produce NO. Further studies should be performed to evaluate the implication of these results in graft patency rates.

Internal mammary artery grafts reactivity in hypertensive patients: role of stretching in extraendothelial nitric oxide.

BACKGROUND: The internal mammary artery (IMA) used in bypass coronary surgery remains efficient for a longer time than other grafts, such as saphenous veins; however, its biological characteristics are incompletely defined. OBJECTIVE: To compare in IMA grafts from hypertensive (HT) and normotensive (NT) patients the presence of endothelium and their functionability, the response to passive stretching and basal tone, the reactivity to exogenous vasoconstrictors, the role of stretching in NO release, and the possible extraendothelial NO source. METHODS AND RESULTS: IMA rings contractility, presence of endothelium, and nitrite release were studied. An endothelial dysfunction associated with hypertension was found. IMA rings from HT had an impaired response to passive stretching, resulting in a decreased relaxation. All IMA grafts had an increased basal tone demonstrated by relaxation to SNP; however, a lesser response was found in HT. Interestingly, it was demonstrated that NO release was present in IMA grafts, despite an endothelial dysfunction and that stretching increased NO release. This effect was inhibited by Ca2+ -free media, L-NAME and a specific neuronal NO synthase (nNOS) inhibitor. Furthermore, the demonstration of the presence of nNOS in smooth muscle cells by immunohistochemistry supports a role of extraendothelial NO. CONCLUSION: We demonstrate the impact of hypertension in IMA grafts producing increased endothelial dysfunction, reduced response to passive stretching, increased basal tone, and impaired responsiveness to exogenous vasoconstrictors and NO release. A specific role of stretching in extraendothelial NO release was demonstrated, which may have an important role in the outcome of IMA grafts due to the protective actions of NO, even in the absence of the endothelium.

Determinación de marcadores séricos de trombosis e inflamación en sujetos con intolerancia a la glucosa: evidencia de un estado protrombótico / Determination of blood markers and inflammation in subjects with impaired glucose tolerance

Objetivo: Este estudio fue diseñado para explorar la presencia de un estado protrombótico, disfunción fibrinolítica e inflamación en sujetos con intolerancia a la glucosa, mediante la evaluación de los marcadores séricos de trombosis, fibrinólisis e inflamación. Métodos: Se estudiaron 48 individuos consecutivos, 25 intolerantes a la glucosa: (nueve hombres y 16 mujeres, 50.0 ±9.2 años) y 23 sujetos control (seis hombres y 17 mujeres, 48.0 ±11 años). Se compararon entre ambos grupos los niveles de dímero-D y fibrinógeno como marcadores de trombosis, el PAI-1 como marcador de fibrinólisis y la proteína C reactiva ultrasensible (PCR-us) como marcador de inflamación. Resultados: En los sujetos intolerantes a la glucosa respecto al grupo control, se observaron diferencias significativas en los marcadores de trombosis: fibrinógeno 317.7 ± 32.1 vs. 266.7 ± 25.4 mg/dL (p<0.0001), dímero-D 489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL (p<0.01) y en el marcador de fibrinólisis PAI-1 66.4 ± 30.7 vs. 35.5 ± 31.0 ng/mL (p<0.006). En el marcador de inflamación, PCR-us no se observó diferencia significativa, respecto al grupo control 0.45 ± 0.6 vs. 0.38 ± 0.4 mg/dL (p<0.28). Conclusiones: Estos resultados sugieren la presencia de un estado protrombótico con disfunción del sistema fibrinolítico, en sujetos intolerantes a la glucosa.

Objective: This study was designed to explore the presence of a prothrombotic state, fibrinolytic dysfunction and infammation in impaired glucose tolerance subjects, by evaluating serum markers of thrombosis, fibrinolysis and infammation. Methods: In 48 consecutive adults, 25 patients with impaired glucose tolerance (nine men and 16 women, 50.0 ±9.2 years) were compared with 23 control subjects (six men and 17 women, 48.0 ±11 years). The markers of thrombotic activation used were D-dimer and fibrinogen. Fibrinolysis dysfuntion was evaluated with plasminogen activator inhibitor 1 (PAI-1) and the infammatory marker studied was hs-C reactive protein (hs-CRP). Results: The markers of thrombotic state were significantly higher in patients with impaired glucose tolerance (IGT) than in controls: D dimer (489.6 ± 277.3 vs. 345.8 ± 158.9 ng/mL) (p < 0.01) and fibrinogen (317.7 ±32.1 vs. 266.7 ±25.4 mg/dL) (p < 0.0001). Fibrinolytic marker PAI-1 also differed significantly between the two study groups (66.4 ± 30.7 vs. 35.5 ± 31.0 ng/ mL) (p < 0.006). However, hs-CRP, as infammation marker, (0.45 ± 0.62 mg/dL vs. 0.38 ± 0.47) did not differ significantly between the two study groups (<0.28). Conclusion: This result suggests the presence of a prothrombotic state with fibrinolytic dysfunction in subjects with impaired glucose tolerance.

Síndromes coronarios agudos sin elevación del segmento ST: ¿Por qué debemos ser intervencionistas? / Acute coronary syndromes without ST elevation

La incidencia de angina inestable e infarto sin onda Q ha crecido dramáticamente. El riesgo de muerte e infarto es alto en las 6 a 8 primeras semanas de admisión. Debe realizarse precozmente la estratificación de riesgo en los portadores de síndromes coronarios agudos. Los estudios VANQWISH y TIMI-III B sugirieron que la mayoría de los pacientes no se benefician con el manejo invasivo precoz de rutina. En el estudio FRISC II, la frecuencia de muerte e infarto a 6 meses fue del 9.4 por ciento con estrategia invasiva vs 12.1 por ciento con estrategia conservadora. La superioridad de la estrategia invasiva, reportada previamente, fue confirmada por el estudio TACTICS-TIMI 18. El punto final primario combinado, a 6 meses, se redujo significativamente en el grupo invasivo: 15.9 por ciento vs 19.4 por ciento con la estrategia conservadora. A mayor riesgo del paciente, mayor fue el beneficio de la estrategia invasiva precoz.Aún no sabemos si hemos alcanzado el límite en términos de mejorar la evolución clínica de los síndromes coronarios agudos con las estrategias disponibles, lo que sí sabemos es que al alta hospitalaria necesitan ser tratados agresivamente, para controlar los factores de riesgo cardiovascular y neutralizar la placa ateroesclerótica vulnerable.

Oxido nítrico en vasos usados para bypass: arteria mamaria vs. venas safena, rol de la tensión de estiramiento / Nitric oxide on bypass glasses: mammary artery vs safena vein, lift strain role

Una estimación de la función endotelial de arterias mamarias (art mam) y venas safenas (vena saf) usadas parabypass coronario sería medir la liberación de oxido nítrico (NO). En nuestro laboratorio observamos, en arterias de conejos, que el estiramiento (stretching) incrementa el NO. Objetivos: Determinar la presencia de endotelio en art mam y vena saf en pacientes (p) de bypass coronario y dosar el contenido de NO. Evaluar el rol del estiramiento. Métodos: Se usaron restos (1-4 anillos) de art mam y vena saf de 44 p del CMC con o sin factores de riesgo (FR) asociados. Se efectuaron dos protocolos in vitro: NT) anillos no tensados (precarga de 0g) y T) anillos tensados (precarga de 2g:art mam o 3g:vena saf). La presencia de endotelio se determinó por relajación (con endotelio) o no (sin endotelio) a acetilcolina 10-6M o bradiquinina 10-7M sobre precontractura con noradrenalina en baño de órgano aislado. El NO se dosó por método de Griess a los 15 min y en una curva de tiempo (90 min) con y sin tratamiento con L-Name 10-3M o Ang II (10-9 a -6M). Resultados: 7 p presentaron endotelio sin asociación con los FR. En T el NO basal fue mayor en vasos con endotelio en art mam (1829±259 vs 3699±65 pmol/mg n=19; p<0,05) y vena saf (694±103 vs 1290±216 pmol/mg, n=18; p<0,01). T estimuló laliberación de NO, este efecto es mayor en art mam con endotelio que en vena saf (p<0,001) y se mantiene aúnen anillos sin endotelio a los 90 min. En NT no hubo diferencias entre art mam y vena saf. Ang II mostródiferencias entre T y NT. L-Name solo inhibió el NO en vena saf con endotelio. Conclusiones: Los vasospresentaron disfunción endotelial generalizada sin asociación con ningún FR. Sin embargo, hubo liberación deNO incluso en anillos sin endotelio. Demostramos mayores niveles de NO en art mam. Sin embargo art mam yvena saf aumentan su liberación si se someten a T y este aumento se mantiene en la disfunción endotelial. Suorigen involucraría activación de la enzima NO Sintetasa neuronal(nNOS). La T activaría la nNOS, situaciónhomologable in vivo a la T que sufriere el vaso injertado en el circuito arterial coronario. Este mecanismocompensador de NO ayudaría a explicar la buena perfomance, aun en vena saf, de los puentes coronarios, más allá del FR asociado.

Ateroesclerosis : ¿por qué una enfermedad inflamatoria?. Fundamentos, marcadores, biología molecular / Atherosclerosis : Why an inflammatory disease?. Basis, markers, molecular biology

En este artículo se resume brevemente el rol de la inflamación en la patogénesis y la fisiopatología de los síndromes coronarios agudos y los avances recientes del conocimiento sobre los factores responsables de la inestabilidad. Se examina la evidencia que sostiene la aseveración de que la inflamación de la placa ateroesclerótica puede jugar un rol clave en la patogénesis de la angina inestable y también los mecanismos a través de los cuales la activación de las células inflamatorias en la placa ateroesclerótica pueden conducir a una oclusión transitoria o permanente. El proceso de aterogénesis ha sido considerado fundamentalmente como la acumulación de lípidos dentro de la pared arterial; sin embargo es mucho más que eso. Las lesiones ateroescleróticas pueden describirse como correspondientes a una enfermedad inflamatoria. De hecho, la más precoz de las lesiones, la llamada estría grasa, es una lesión puramente inflamatoria, constituída sólo por macrófagos derivados de monocitos y linfocitos T. Se discute el uso de marcadores bioquímicos para la identificación y estratificación precoz de riesgo. La evaluación temprana del riesgo es esencial para la aplicación del tratamiento apropiado y el manejo futuro de pacientes con síndromes coronarios agudos. La proteína C reactiva, un reactante de fase aguda, es un marcador sensible de inflamación, y es un buen candidato para conocer el riesgo de futuros eventos cardiovasculares. La interacción adhesiva es un prerequisito para el normal funcionamiento de todos los componentes del sistema cardiovascular, sin embargo también está involucrada en la patogénesis de la enfermedad cardiovascular. Existe creciente evidencia de que las moléculas de adhesión (integrinas, selectinas y la superfamilia de las inmunoglobulinas) juegan un importante rol en la patología cardiovascular. Datos experimentales y epidemiológicos sugieren que la disyunción endotelial, luego de una infección o una inflamación, puede ser un factor de riesgo transitorio para enfermedad cardiovascular, que podría promover una respuesta vascular anormal. La disrupción, fisura o ruptura de placa, complican el curso de la ateroesclerosis coronaria. El riesgo de disrupción de una placa depende más de su composición que del tamaño de la placa y de la severidad de la estenosis...