Aortic stenosis (AS) is the most common valvular heart disease in ageing populations and is associated with substantial morbidity and mortality. Despite advances in surgical and transcatheter valve replacement, no medical therapy has yet been shown to prevent disease onset or slow progression. Calcific AS is now recognised as an active, multifactorial process involving lipid infiltration, inflammation and osteogenic calcification of the aortic valve. Lipoprotein(a) has emerged as a key contributor to these mechanisms and is a genetically determined, lifelong cardiovascular risk factor. Lipoprotein(a) is a major carrier of oxidised phospholipids, which promote valvular inflammation and calcification. Epidemiological and Mendelian randomisation studies consistently demonstrate a strong and likely causal association between elevated lipoprotein(a) and AS. Experimental and translational data suggest that lipoprotein(a) exerts its effects early in the disease course, promoting valve inflammation and calcification before significant stenosis develops. The recent development of lipoprotein(a)-lowering therapies has renewed interest in targeting this pathway, raising the possibility that early lipoprotein(a)-lowering may modify disease progression, a hypothesis now being tested in clinical trials.
Antiplatelet pretreatment in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) is controversial. It is vital that the risk of ischaemia and the risk of haemorrhage are both considered when managing this patient group. Current clinical guidelines do not recommend routine pretreatment in patients presenting with NSTE-ACS who are having coronary angiography within 24 hours. However, a significant portion of these patients will not have coronary angiography until after 24 hours. Pretreatment with antiplatelets may reduce the risk of ischaemic events, but it is associated with bleeding and delays to coronary artery bypass grafting, and it may be deleterious in patients with diagnoses other than NSTE-ACS, such as acute aortic syndromes, pulmonary embolism or intracranial bleeds. This review analyses the most important studies assessing antiplatelet pretreatment in NSTE-ACS.
