Subclinical Thyroid Dysfunction and the Risk of Heart Failure Events: An Individual Participant Data Analysis From 6 Prospective Cohorts

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.     

Aspiration thrombectomy during primary percutaneous coronary intervention as adjunctive therapy to early (in-ambulance) abciximab administration in patients with acute ST elevation myocardial infarction: an analysis from Leiden MISSION! acute myocardial infarction treatment optimization program

Background: The benefits of early abciximab administration and thrombus aspiration in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) have previously been elaborated. However, whether there is an adjunctive effect of thrombus aspiration among STEMI patients, with angiographic evidence of thrombus, receiving early prehospital abciximab remains unclear. Methods: In the context of a fixed protocol for PPCI, 158 consecutive patients with STEMI were enrolled, in whom abciximab was started early before hospital arrival (in‐ambulance); 79 patients who had PPCI with thrombus aspiration (thrombectomy‐facilitated PCI group), were compared to 79 who had PPCI without thrombus aspiration (conventional PCI group) in a prospective nonrandomized study. The primary end‐point was complete ST‐segment resolution within 90 minutes. Secondary end points included distal embolization, enzymatic infarct size as well as left ventricular ejection fraction (LVEF) assessed by gated single‐photon emission computed tomography. Major adverse cardiac events (MACEs) were evaluated up to 12 months. Results: Both groups were comparable for baseline characteristics. ST‐segment resolution was significantly higher in the thrombectomy‐facilitated group (P = 0.002), and multivariate analysis identified thrombectomy as an independent predictor of ST‐segment resolution (OR = 9.4, 95% CI = 2.6–33.5, P = 0.001). Distal embolization was higher in the conventional PCI group among patients with higher thrombus grades. No difference was observed between both groups in infarct size assessed by peak creatine kinase (p = 0.689) and peak Tn‐T levels (P = 0.435). Also, the LVEF at 3 months was similar (P = 0.957). At 12 month clinical follow‐up, thrombus aspiration was, however, associated with reduced all‐cause mortality (log‐rank p = 0.032). Conclusion: Among STEMI patients treated with PPCI and in‐ambulance abciximab, it appears that a selective strategy of thrombus aspiration still has additive benefit. (J Interven Cardiol 2012;25:1–9)     

Management of acute coronary syndrome: achievements and goals still to pursue. Novel developments in diagnosis and treatment

Acute coronary syndromes contribute a substantial part of the global disease burden. To realize a reduction in mortality and morbidity, the management of patients with these conditions involves the integration of several different approaches. Timely delivery of appropriate care is a key factor, as the beneficial effect of reperfusion is greatest when performed as soon as possible. Innovations in antithrombotic therapy have also contributed significantly to improvements in the prevention of ischaemic complications. However, with the use of such treatment, an increase in the risk of bleeding is inevitable. Therefore, the greatest challenge is now to obtain an optimal balance between the prevention of ischaemic complications and the risk of bleeding. In this regard, identification of patients at highest risk of either one is essential.     

Association of atherosclerosis in the descending thoracic aorta with coronary artery disease on multi detector row computed tomography coronary angiography in patients with suspected coronary artery disease

The association between atherosclerosis in the descending thoracic aorta (DTA) visualized on computed tomography coronary angiography (CTA) and coronary artery disease (CAD) has not been extensively explored. Therefore, a comprehensive analysis of DTA atherosclerosis on CTA was performed and the association of DTA atherosclerosis with CAD was evaluated in patients with suspected CAD. A total of 344 patients (54 ± 12 years, 54 % men) with suspected CAD underwent CTA. CTA were classified based on CAD severity in no signs of atherosclerosis or minor wall-irregularities <30 %, non-significant CAD 30–50 %, or significant CAD ≥50 % stenosis. The DTA was divided in segments according the posterior intercostal arteries. Per segment the presence of atherosclerotic plaque (defined as ≥2 mm wall thickness) was determined and maximal wall thickness was measured. Plaque composition was scored as non-calcified or mixed and the percentage of DTA segments with atherosclerosis was calculated. Significant CAD was present in 152 (44 %) patients and 278 (81 %) had DTA atherosclerotic plaque. DTA maximal wall thickness and percentage of DTA segments with atherosclerosis were 2.7 ± 1 mm and 49 ± 36 %. The presence, severity and extent of DTA atherosclerosis significantly increased with increasing CAD severity. Multivariate logistic regression analysis corrected for age and other risk factors demonstrated independent associations of DTA plaque (OR 6.56, 95 % CI 1.78–24.19, p = 0.005) and maximal DTA wall thickness (OR 2.00, 95 % CI 1.28–3.12, p = 0.002) with significant CAD. The presence and severity of DTA atherosclerosis were independently related with significant CAD on CTA in patients with suspected CAD.     

Raman spectroscopic investigation of atorvastatin,amlodipine, and both on atherosclerotic plaque development in APOE*3 Leiden transgenic mice

Raman spectroscopy allows quantitative, non-destructive evaluation of entire, intact atherosclerotic plaques. We quantified the anti-atherosclerotic effects of atorvastatin and amlodipine on progression of atherosclerosis using post-mortem Raman spectroscopic plaque imaging in 28 APOE*3 Leiden transgenic mice who were fed a high fat/high cholesterol diet for 28 weeks. Mice were assigned to a control group receiving the diet alone or to groups that received the diet with either 0.01% w/w atorvastatin, 0.002% w/w amlodipine, or the combination. The entire excised aortic arch was scanned with Raman microspectroscopy for quantitation of the distribution of cholesterol and calcification content. When mice had been treated with atorvastatin, cholesterol accumulation and calcification in the aortic arch was reduced by 91 and 98%, respectively, (both P<0.001). Amlodipine did not reduce the cholesterol content but reduced calcification of the aorta by 69% (P<0.05). The combination of amlodipine and atorvastatin was as effective as atorvastatin alone. This study demonstrates the strong atheroprotective potential of atorvastatin. In addition it is demonstrated that amlodipine reduces mineralization of atherosclerotic plaque. No synergistic effect of the combination of amlodipine and atorvastatin on plaque development is demonstrated. This study encourages Raman spectroscopic evaluations of anti-atherosclerotic drugs in larger animals and humans in vivo.