Elisabeth von der Lohe

C-reactive protein and fibrin clot strength measured by thrombelastography after coronary stenting.

Inflammation is implicated in the progression of coronary artery disease and the molecular processes of inflammation and thrombosis are closely intertwined. Elevated levels of C-reactive protein (CRP) have been associated with an elevated risk of adverse ischaemic events after coronary stenting and hypercoagulability. Heightened whole blood clot strength measured by thrombelastography (TEG) has been associated with adverse ischaemic events after stenting. We intended to examine the relationship of CRP to plasma fibrin clot strength in patients after coronary stenting. Plasma fibrin clot strength was measured by TEG in 54 patients 16–24 h after undergoing elective percutaneous coronary intervention (PCI). Coagulation was induced in citrated plasma by addition of kaolin and CaCl2. Plasma levels of CRP and fibrinogen were measured by enzyme-linked immunoassay. Increasing quartiles of CRP were associated with increasing levels of maximal plasma fibrin clot strength measured by TEG (P < 0.001) and increasing BMI (P = 0.04). Patients in the highest quartile of CRP had significantly higher maximal fibrin clot strength (G) than the patients in the lowest quartile (G: 3438 ± 623 vs. 2184 ± 576 dyn/cm2, P < 0.0001). Fibrinogen concentration was not significantly different across quartiles of CRP (P = 0.97). Patients with established coronary artery disease undergoing coronary stenting who have elevated CRP after PCI exhibit heightened maximal plasma fibrin clot strength as compared with those with low CRP. Thrombotic risk associated with elevated CRP may be linked to procoagulant changes and high tensile fibrin clot strength independent of fibrinogen concentration.

Takotsubo cardiomyopathy in a patient with esophageal cancer: a case report

IntroductionTakotsubo cardiomyopathy has increasingly been reported in the medical literature in recent years. Much is still unknown regarding risk factors and clinical relationships. We contribute this case report to the growing set of literature on the topic.Case presentationWe report the case of a 64-year-old woman with esophageal cancer who developed takotsubo cardiomyopathy, a form of reversible heart failure, and we present a review of the literature. Patients present with symptoms similar to an acute coronary syndrome; however, cardiac catheterization reveals patent coronary arteries, and symptoms of heart failure resolve completely within weeks.ConclusionIt is important that clinicians consider takotsubo cardiomyopathy in the differential diagnosis of heart failure and gain a basic understanding of the clinical presentation and diagnosis.

Protease Activated Receptor-1 (PAR-1) Mediated Platelet Aggregation is Dependant on Clopidogrel Response

INTRODUCTION Clopidogrel inhibits ADP mediated platelet aggregation through inhibition of the P2Y12 receptor by its active metabolite. Thrombin induces platelet aggregation by binding to protease activated receptor-1 (PAR-1), and inhibition of PAR-1 has been evaluated in patients treated with clopidogrel to reduce ischemic events after acute coronary syndromes. Residual PAR-1 mediated platelet aggregation may be dependent on extent of clopidogrel response. MATERIAL AND METHODS Platelet aggregation was measured in 55 patients undergoing elective PCI at 16-24 hours after 600 mg clopidogrel loading dose by light transmittance aggregometry using ADP 20 μM and thrombin receptor agonist peptide (TRAP) at 15 μM and 25 μM as agonists. Genomic DNA was genotyped for common CYP2C19 variants. RESULTS Increasing quartiles of 20 μM ADP induced platelet aggregation after clopidogrel loading were associated with increasing levels of TRAP mediated platelet aggregation. Patients in the highest quartile (clopidogrel non-responders) of post treatment ADP aggregation had significantly higher TRAP mediated aggregation than the patients in the lowest quartile (clopidogrel responders) [TRAP 15 μM: 79.6 ± 5% vs. 69.5 ± 8%, p<0.001]. CONCLUSIONS Non-responders to clopidogrel show increased residual platelet aggregation induced by TRAP, whereas clopidogrel responders exhibit attenuated response to TRAP. Addition of PAR-1 antiplatelet drugs may be most effective in patients with reduced clopidogrel response and high residual TRAP mediated platelet aggregation.

Combined distal embolization protection and rheolytic thrombectomy to facilitate percutaneous revascularization of totally occluded saphenous vein grafts

Totally occluded saphenous vein grafts are difficult to treat percutaneously with a higher likelihood of distal embolization and slow‐flow or no‐reflow during percutaneous interventions. The PercuSurge system, which utilizes a distal balloon occlusive device, has been shown to improve clinical outcomes during saphenous vein graft (SVG) interventions. This device may not be optimal in the setting of heavy thrombus or debris burden, a situation frequently encountered in totally occluded SVGs. Rheolytic thrombectomy facilitates percutaneous interventions by effectively removing intraluminal thrombus and debris but lacks distal embolization protection. We report our experience with the synergistic use of balloon‐based distal embolization protection (PercuSurge) and rheolytic thrombectomy (AngioJet) to optimize percutaneous revascularization of totally occluded SVGs. Catheter Cardiovasc Interv 2003;60:212–217.

Prediction of Ischemic Events after Percutaneous Coronary Intervention: Thrombelastography Profiles and Factor XIIIa Activity

Background  High plasma fibrin clot strength (MA) measured by thrombelastography (TEG) is associated with increased risk of cardiac events after percutaneous coronary interventions (PCIs). Factor XIIIa (FXIIIa) cross-links soluble fibrin, shortens clot formation time (TEG-K), and increases final clot strength (MA). Methods  We analyzed platelet-poor plasma from patients with previous PCI. Kaolin-activated TEG (R, K, MA) in citrate platelet-poor plasma and FXIIIa were measured ( n  = 257). Combined primary endpoint was defined as recurrent myocardial infarction (MI) or cardiovascular death (CVD). Relationship of FXIIIa and TEG measurements on cardiac risk was explored. Results  FXIIIa correlated with TEG-MA ( p  = 0.002) and inversely with TEG-K ( p  < 0.001). High MA (≥35.35 mm; p  = 0.001), low K (<1.15 min; p  = 0.038), and elevated FXIIIa (≥83.51%; p  = 0.011) were associated with increased risk of CVD or MI. Inclusion of FXIIIa activity and low TEG-K in risk scores did not improve risk prediction as compared with high TEG-MA alone. Conclusion  FXIIIa is associated with higher plasma TEG-MA and low TEG-K. High FXIIIa activity is associated with a modest increase in cardiovascular risk after PCI, but is less sensitive and specific than TEG-MA. Addition of FXIIIa does not provide additional risk stratification beyond risk associated with high fibrin clot strength phenotype measured by TEG.

Cardiovascular Risk Factors and the Development of Coronary Heart Disease in Women

The following risk factors are associated with a high prevalence of coronary heart disease, both in men and women: Age Family history of coronary heart disease Smoking Hypertension Dyslipidemia Diabetes mellitus

Primary and Secondary Prevention of Coronary Heart Disease

In view of the prevalence of coronary heart disease and the fact that it remains the leading cause of death in the twenty-first century the public health importance of both primary and secondary prevention is obvious. Prevention of even a small percentage of coronary heart disease would not only have a significant impact on reduction in cardiovascular mortality,but also substantially reduce health care costs.

Coronary Artery Bypass Surgery

Each year 300,000 coronary artery bypass grafting (CABG) operations are performed in the United States, 25% of them in women. Over the past 30 years the patient population undergoing surgery has dramatically changed. In the early 1970s only a few patients (men and women) over the age of 70 years and/or with an ejection fraction less than 50% were felt to be suitable candidates for CABG. With refinements in technology and increasing operator experience the percentage of high-risk patients significantly rose (Weintraub et al. 1998). In other words, presently there is a much higher percentage of patients with reduced left ventricular function, three-vessel coronary artery disease, diabetes mellitus, and over 70 years of age that undergo CABG than 25 years ago. Due to the increasing number of high-risk patients, operative mortality in men rose from 1% in 1974 to 2.7% in 1991 and in women from 1.3 to 5.4%, respectively. Since coronary artery disease in women generally presents approximately 10–15 years later in life than it does in men women undergoing CABG surgery are significantly older than men. The percentage of men older than 60 years increased from 28.8% in 1974–1979 to 59.6% in 1988–1991. The percentage of women over age 60 years was 45.1% from 1974–1979 and 77.3% from 1988–1991. Only 3.5% of men, but 7.3% of women, were older than 70 years from 1974 to 1979. From 1988 to 1991 it was 24.3 and 38.8%, respectively.

Hormone Replacement Therapy

Coronary heart disease continues to be an infrequent disease in premenopausal women, even in women with diabetes mellitus; however, after menopause (the time when estrogen production decreases) the prevalence of coronary heart disease in women increases with increasing age and reaches that of men by age 75 years. Women with premature menopause (<35 years of age) regardless of etiology (either natural or after ovariectomy) have a twofold higher risk of coronary heart disease (Wenger et al. 1993). These findings led to the conclusion that estrogens are cardioprotective and play a major role for the low prevalence of cardiovascular disease in pre-menopausal women; however, the role of estrogen (and other hormones) in the pathogenesis of coronary heart disease is still under investigation.

Pathophysiology of Coronary Heart Disease and the Effects of Estrogen

Atherosclerosis of the coronary arteries is the underlying pathophysiological mechanism of coronary heart disease (CHD) and is the same for both genders. There are numerous different theories with regard to the genesis of atherosclerosis. The most commonly held and most credible theory is the “response-to-injury” hypothesis by R. Ross according to which various types of injuries in the endothelium and in vascular smooth muscle cells (SMCs) lead to an exaggerated inflammatory fibroproliferative reaction in the vessel wall with subsequent plaque formation.