Sex differences in characteristics and outcome in acute coronary syndrome patients in the Netherlands

Background Sex differences in acute coronary syndrome (ACS) have been reported, but little is known about the situation in the Netherlands. M

Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: rationale and design of the LEGACY study

BackgroundEarly aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI.MethodsThe LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT.ConclusionsThe LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.Cardiolog

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: comments from the Dutch ACS working group

On behalf of the Dutch ACS working group, we discuss multiple recommendations which have been implemented in the 2015 ESC guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevatio

Cannabinoid receptor type 1 protects against age-related bone loss by regulating osteoblast and adipocyte differentiation of bone marrow stromal cells

Osteoporosis is characterised by reduced bone formation with replacement of the bone marrow compartment by fat, due to an age-dependent reduction in osteoblast differentiation and a reciprocal increase in adipocyte differentiation. Here we report that the type 1 cannabinoid receptor (CB1) regulates this process to protect against age related bone loss. Mice with CB1 deficiency (CB1<sp>-/-</sp>) had a increased peak bone mass when compared with wild type littermates (females; 28% increase and males 14% increase) due to a reduction in bone resorption. However, CB1<sp>-/-</sp> mice developed an accelerated age-related osteoporosis characterised by reduced bone formation and a dramatic accumulation of fat in the bone marrow (BM) compartment. Studies <i>in vitro</i> showed that bone nodule formation was reduced by 45% in marrow stromal cells from CB1<sp>-/-</sp> mice when compared with wild type littermates (p<0.05) and expression of Runx2, alkaline phosphatase and osteopontin were reduced. Conversely, adipocyte differentiation was increased by 30% (p<0.02) in marrow stromal cultures from CB1<sp>-/-</sp> mice when compared with wild type. Adipocyte cultures from CB1<sp>-/-</sp> mice showed enhanced insulin-induced AKT activation and increased expression of the adipocyte-specific genes PPAR gamma and C/EBP when compared with wild type. Adipocyte differentiation was increased in wild type BM cultures exposed to the CB1 selective antagonist AM251, but these effects were blocked by the cannabinoid receptor agonist CP55,490 and the Gi/o inhibitor pertussis toxin, consistent with a CB1 mediated effect. Intracellular cAMP levels were elevated in stromal cells cultured from CB1<sp>-/-</sp> mice and these cells exhibited increased enhanced phosphorylation of the cAMP response element transcription factor CREB. The CB agonist CP55,490 inhibited cAMP accumulation in 3T3-L1 pre-adipocytes and this effect was reversed by AM251 and pertussis toxin. Furthermore, exposure of wild type stromal cells to AM251 was sufficient to stimulate adipogenesis in the absence of the phosphodiesterase inhibitor IBMX. Taken together, these observations indicate that CB1 regulates the commitment of mesenchymal stem cells to differentiate into osteoblasts and adipocytes by a cAMP mediated mechanism. The CB1 pathway therefore plays a unique role in bone metabolism by restraining peak bone mass through effects on osteoclast differentiation but by protecting against age-related bone loss by regulating adipocyte and osteoblast differentiation

Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction

Objectives To evaluate the extent of platelet aggregation inhibition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), treated with different antiplatelet agents and dosages. Background The extent of platelet aggregation inhibition is an independent predictor of major cardiac events after elective PCI. In STEMI patients undergoing PCI, routine dose of antiplatelet agents may be associated with less effective platelet aggregation inhibition. Methods Patients were treated with clopidogrel before angiography and randomized to abciximab, tirofiban, high-dose tirofiban, or no glycoprotein (GP) IIb/IIIa inhibitor; GP IIb/IIIa inhibitor bolus, followed by maintenance infusion, was administered after angiography, but before PCI. Platelet aggregation inhibition was assessed before angiography, immediately after PCI, and 1 and 6 h afterwards. Results The total study population consisted of 112 patients. Platelet aggregation inhibition was variable for individuals and suboptimal for all agents, particularly in the periprocedural period. Only with high-dose tirofiban, mean periprocedural platelet aggregation inhibition exceeded 80%. Angiographic parameters after PCI were not different between the groups. No relationship was found between the level of platelet aggregation and parameters of PCI success (Thrombolysis In Myocardial Infarction frame count and myocardial blush grade), after combining the data from all four groups studied. Conclusions Platelet aggregation inhibition in STEMI patients undergoing PCI, treated with antiplatelet agents, is variable and suboptimal for all agents and dosages studied. Only with high-dose tirofiban, mean periprocedural platelet aggregation inhibition exceeded 80%. However, no relationship of platelet aggregation inhibition and angiographic outcome was found in this patient cohort

Indications for an early invasive strategy in NSTE-ACS patients

An early invasive strategy in patients who have acute coronary syndrome without ST-elevation (NSTE-ACS) can improve clinical outcome in high-risk subgroups. According to the current guidelines of the European Society of Cardiology (ESC), the majority of NSTE-ACS patients are classified as "high-risk". We propose to prioritise patients with a global registry of acute coronary events (GRACE) risk score >140 over patients with isolated troponin rise or electrocardiographic changes and a GRACE risk score <140. We also acknowledge that same-day transfer for all patients at a high risk is not necessary in the Netherlands since the majority of Dutch cardiology departments are equipped with a catheterisation laboratory where diagnostic coronary angiography is routinely performed in NSTE-ACS patients. Therefore, same-day transfer should be restricted to true high-risk patients (in addition to those NSTE-ACS patients with very high-risk (VHR) criteria) in centres without coronary angiography capabilities.Cardiolog

The effect of raloxifene on bone marrow adipose tissue and bone turnover in postmenopausal women with osteoporosis

Bone and mineral researc