BACKGROUNDIschemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. METHODSIn this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit. RESULTSAt 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points. CONCLUSIONSAmong patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.

IMPORTANCE Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking.OBJECTIVE To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy. DESIGN, SETTING, AND PARTICIPANTSA prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019.INTERVENTIONS Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery.MAIN OUTCOMES AND MEASURES Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year.RESULTS At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64). CONCLUSIONS AND RELEVANCEIn this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes. TRIAL REGISTRATION trialregister.nl Identifier: NTR4973

C-reactive protein (CRP) has been postulated to play a causal part in atherosclerosis and its acute complications. We assessed the effects of CRP-infusion on coagulation and inflammatory pathways to determine its role in atherothrombotic disease. Seven male volunteers received an infusion on two occasions, containing 1.25 mg/kg recombinant human CRP (rhCRP) or diluent, respectively. CRP-concentrations rose after rhCRPinfusion from 1.9 (0.3 to 8.5) to 23.9 (20.5 to 28.1) mg/L, and subsequently both inflammation and coagulation were activated. This sequence of events suggests that CRP is not only a well known marker of cardiovascular disease, but is also probably a mediator of atherothrombotic disease. C -reactive protein (CRP) has emerged as an independent predictor of cardiovascular risk in various clinical settings. [1][2][3] Evidence showing direct prothrombotic and inflammatory effects of CRP in vitro 4 -6 has led to the concept that CRP might be an active mediator of atherothrombotic events. Although direct pathophysiological functions of CRP itself are a matter of debate, experimental observations from mice transgenic for human CRP have suggested a contributive role of CRP in the development of cardiovascular complications. 7,8 To date, no in vivo data in humans exist to support a direct atherogenic action of CRP. In the present study, we assessed the effects of rhCRP-infusion on established pathways in cardiovascular disease progression, including inflammation and coagulation in healthy male volunteers. Materials and MethodsSeven healthy, nonsmoking men, aged 33 (26 to 51) years, were included in this study after written informed consent was obtained.None of the volunteers had febrile illness or cardiovascular disease or were on medication. After an overnight fast, a bolus of highly purified rhCRP was given intravenously at a dose of 1.25 mg per kg body weight. Blood was drawn at baseline and 1, 4, 8, and 24 hours after infusion. After 4 weeks, a time-control study was performed using the CRP-free diluent. The study was approved by the institutional review board of the Academic Medical Center Amsterdam.The rhCRP (BiosPacific), derived from Escherichia coli (K12, substrain NM522), was supplied in 20 mmol/L Tris, 140 mmol/L NaCL, 2 mmol/L CaCl 2 , pH 7.5, and 0.05% (wt/vol) sodium azide and revealed a single 23-kDa band (Ͼ99%) after CBBR-staining (1 g; SDS-polyacrylamide gel). Before purification, the host cell protein concentration was 85 ppm, as determined by a high-sensitive ELISA in accordance with manufacturers' instructions (Cygnus Technologies Inc). Subsequently, the rhCRP was purified using size exclusion chromatography to remove contaminants including endotoxin and sodium azide (Univalid bv). Purity as well as stability were evaluated using sequential highperformance liquid chromatography and time-of-flight mass spectrometry, showing no other protein fractions, including the monomeric variant of CRP, besides the CRP pentamer. Endotoxin levels were below 1.5 endotoxin units (EU)/mL as evaluated by Li...

No abstract

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes ( P <0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events ( P =0.049) and a 21% additional risk reduction for heart failure ( P =0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.

Abstract-Flavanol-rich cocoa products have been reported to lower blood pressure. It has been suggested that theobromine is partially responsible for this effect. We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure. In a double-blind, placebo-controlled 3-period crossover trial we assigned 42 healthy individuals (age 62Ϯ4.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg and low added cardiovascular risk to a random treatment sequence of dairy drinks containing placebo, flavanol-rich cocoa with natural dose consisting of 106 mg of theobromine, or theobromineenriched flavanol-rich cocoa with 979 mg of theobromine. Treatment duration was 3 weeks with a 2-week washout. The primary outcome was the difference in 24-hour ambulatory systolic blood pressure between placebo and active treatment after 3 weeks. The difference in central systolic blood pressure between placebo and active treatment was a secondary outcome. Treatment with theobromine-enriched cocoa resulted in a meanϮSE of 3.2Ϯ1.1 mm Hg higher 24-hour ambulatory systolic blood pressure compared with placebo (PϽ0.01). In contrast, 2 hours after theobromineenriched cocoa, laboratory peripheral systolic blood pressure was not different from placebo, whereas central systolic blood pressure was 4.3Ϯ1.4 mm Hg lower (Pϭ0.001). Natural dose theobromine cocoa did not significantly change either 24-hour ambulatory or central systolic blood pressure compared with placebo. In conclusion, theobromine-enriched cocoa significantly increased 24-hour ambulatory systolic blood pressure while lowering central systolic blood pressure. (Hypertension. 2010;56:839-846.)Key Words: cocoa Ⅲ theobromine Ⅲ blood pressure Ⅲ hemodynamics Ⅲ aortic pressure waveform T he consumption of foods and beverages rich in flavanols has been associated with a decreased risk of cardiovascular morbidity and mortality. [1][2][3] In Western society, a large proportion of flavanol intake is through cocoa and cocoacontaining products. One of the mechanism by which cocoa could exert its presumed beneficial effects on cardiovascular disease is by lowering blood pressure (BP). There is, however, discussion about the BP-lowering potential of cocoa. A recent meta-analysis of intervention studies looking at the BP-lowering effect of flavanol-rich cocoa found a significant reduction of 4.5 mm Hg for systolic BP (SBP) and 2.5 mm Hg for diastolic BP (DBP). 4 However, most of the clinical trials in the analysis lacked adequate control treatment, and studies that included a proper control group all showed a neutral effect on DBP and SBP. [5][6][7] Other than a possible effect on peripheral (brachial) BP, cocoa intake may improve central hemodynamics. Central BP is thought to be an important determinant of hypertensive organ damage and might be superior to peripheral BP in predicting cardiovascular disease. 8 In a cross-sectional study in healthy individuals, increasing amounts of cocoa consumption...

Carriers of LCAT gene mutations exhibit increased carotid atherosclerosis, indicating an increased risk of cardiovascular disease. The present findings imply that increasing LCAT activity may be an attractive target in cardiovascular prevention strategies.

Abstract-Fabry disease is an X-linked hereditary lysosomal storage disorder attributed to a deficiency of α-galactosidaseA leading to increased plasma levels of globotriaosylsphingosine (lysoGb3 01).In women and atypical patients these vascular parameters were comparable with controls. Pulse wave velocity was not different; advanced glycation end products were only slightly increased in atypical patients. In classically affected women, a small increase in lysoGb3 was associated with an increase in IMT independent of age.In the classically affected men, all with increased IMT and high levels of plasma lysoGb3, lysoGb3 levels did not add to a higher IMT, suggestive of a ceiling effect. For FMD, elevated lysoGb3 levels (>7 nmol/L) contributed to a 2.9% lower FMD independent of age and sex (P=0.02). Increased carotid IMT and decreased brachial FMD occur in classic Fabry disease, which is associated with plasma lysoGb3 level independent of age and sex. These observations still exist despite enzyme replacement therapy. (Hypertension. 2012;60:998-1005.)