Many patients with chest pain undergoing coronary angiography do not show significant obstructive coronary lesions. A substantial proportion of these patients have abnormalities in the function and structure of coronary microcirculation due to endothelial and smooth muscle cell dysfunction. The coronary microcirculation has a fundamental role in the regulation of coronary blood flow in response to cardiac oxygen requirements. Impairment of this mechanism, defined as coronary microvascular dysfunction (CMD), carries an increased risk of adverse cardiovascular clinical outcomes. Coronary endothelial dysfunction accounts for approximately two-thirds of clinical conditions presenting with symptoms and signs of myocardial ischemia without obstructive coronary disease, termed “ischemia with non-obstructive coronary artery disease” (INOCA) and for a small proportion of “myocardial infarction with non-obstructive coronary artery disease” (MINOCA). More frequently, the clinical presentation of INOCA is microvascular angina due to CMD, while some patients present vasospastic angina due to epicardial spasm, and mixed epicardial and microvascular forms. CMD may be associated with focal and diffuse epicardial coronary atherosclerosis, which may reinforce each other. Both INOCA and MINOCA are more common in females. Clinical classification of CMD includes the association with conditions in which atherosclerosis has limited relevance, with non-obstructive atherosclerosis, and with obstructive atherosclerosis. Several studies already exist which support the evidence that CMD is part of systemic microvascular disease involving multiple organs, such as brain and kidney. Moreover, CMD is strongly associated with the development of heart failure with preserved ejection fraction (HFpEF), diabetes, hypertensive heart disease, and also chronic inflammatory and autoimmune diseases. Since coronary microcirculation is not visible on invasive angiography or computed tomographic coronary angiography (CTCA), the diagnosis of CMD is usually based on functional assessment of microcirculation, which can be performed by both invasive and non-invasive methods, including the assessment of delayed flow of contrast during angiography, measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), evaluation of angina induced by intracoronary acetylcholine infusion, and assessment of myocardial perfusion by positron emission tomography (PET) and magnetic resonance (CMR).

Background: About a third of patients with acute stroke and no prior diagnosis of diabetes have hyperglycaemia during the acute phase of stroke. Whether this is an acute stress response or a reflection of underlying diabetes is controversial. Aim: To assess whether impaired glucose metabolism in patients with acute ischaemic stroke and no previous diagnosis of diabetes persists after 3 months, and whether such persistence can be predicted. Design: Prospective observational study. Methods: We enrolled 106 patients with acute ischaemic stroke and no history of diabetes. Fasting blood glucose, serum insulin and the insulin resistance index HOMA were recorded during hospital stay. A standard oral glucose tolerance test was performed at discharge and 3 months later. Results: Ten patients did not complete the study. Eighty-one patients (84.4%) had abnormal glucose metabolism at discharge and 62 (64.6%) after 3 months. Thirty-seven (38.5%) had impaired glucose tolerance at discharge and 26 (27.1%) after 3 months. Forty-four (45.8%) had diabetes at discharge, and 36 (37.5%) at 3 months. Post-load hyperglycaemia at discharge was a predictor of diabetes after 3 months. A plasma glucose cut-off of 11.7 mmol/l (210 mg/dl) had a specificity of 90.0% and a positive predictive value of 81.3%. HOMA increased progressively from patients with normal glucose metabolism to those with newly diagnosed diabetes. Discussion: Impaired glucose tolerance and previously unrecognized diabetes could be detected early in the stroke course, and persisted after 3 months in more than two-thirds of our patients. Post-load hyperglycaemia during the acute phase of stroke may be useful in identifying patients with abnormal glucose metabolism, which places them at risk for adverse outcomes, including cardiovascular disease.

Objectives To determine whether there is a relation between statin utilisation and coronary heart disease (CHD) mortality in populations with different levels of coronary risk, and whether the relation changes over time. Design Ecological study using national databases of dispensed medicines and mortality rates. Setting Western European countries with similar public health systems. Main outcome measures Population CHD mortality rates (rate/100 000) as a proxy for population coronary risk level, and statin utilisation expressed as Defined Daily Dose per one Thousand Inhabitants per Day (DDD/TID), in each country, for each year between 2000 and 2012. Spearman's correlation coefficients between CHD mortality and statin utilisation were calculated. Linear regression analysis was used to assess the relation between changes in CHD mortality and statin utilisation over the years. Results 12 countries were included in the study. There was a wide range of CHD mortality reduction between the years 2000 and 2012 (from 25.9% in Italy to 57.9% in Denmark) and statin utilisation increase (from 121% in Belgium to 1263% in Denmark). No statistically significant relations were found between CHD mortality rates and statin utilisation, nor between changes in CHD and changes in statin utilisation in the countries over the years 2000 and 2012. Conclusions Among the Western European countries studied, the large increase in statin utilisation between 2000 and 2012 was not associated with CHD mortality, nor with its rate of change over the years. Factors different from the individual coronary risk, such as population ageing, health authority programmes, guidelines, media attention and pharmaceutical industry marketing, may have influenced the large increase in statin utilisation. These need to be re-examined with a greater emphasis on prevention strategies.

Strategies to prevent acute coronary and cerebrovascular events are based on accurate identification of patients at increased cardiovascular (CV) risk who may benefit from intensive preventive measures. The majority of acute CV events are precipitated by the rupture of the thin cap overlying the necrotic core of an atherosclerotic plaque. Hence, identification of vulnerable coronary lesions is essential for CV prevention. Atherosclerosis is a highly dynamic process involving cell migration, apoptosis, inflammation, osteogenesis, and intimal calcification, progressing from early lesions to advanced plaques. Coronary artery calcification (CAC) is a marker of coronary atherosclerosis, correlates with clinically significant coronary artery disease (CAD), predicts future CV events and improves the risk prediction of conventional risk factors. The relative importance of coronary calcification, whether it has a protective effect as a stabilizing force of high-risk atherosclerotic plaque has been debated until recently. The extent of calcium in coronary arteries has different clinical implications. Extensive plaque calcification is often a feature of advanced and stable atherosclerosis, which only rarely results in rupture. These macroscopic vascular calcifications can be detected by computed tomography (CT). The resulting CAC scoring, although a good marker of overall coronary plaque burden, is not useful to identify vulnerable lesions prone to rupture. Unlike macrocalcifications, spotty microcalcifications assessed by intravascular ultrasound or optical coherence tomography strongly correlate with plaque instability. However, they are below the resolution of CT due to limited spatial resolution. Microcalcifications develop in the earliest stages of coronary intimal calcification and directly contribute to plaque rupture producing local mechanical stress on the plaque surface. They result from a healing response to intense local macrophage inflammatory activity. Most of them show a progressive calcification transforming the early stage high-risk microcalcification into the stable end-stage macroscopic calcification. In recent years, new developments in noninvasive cardiovascular imaging technology have shifted the study of vulnerable plaques from morphology to the assessment of disease activity of the atherosclerotic lesions. Increased disease activity, detected by positron emission tomography (PET) and magnetic resonance (MR), has been shown to be associated with more microcalcification, larger necrotic core and greater rates of events. In this context, the paradox of increased coronary artery calcification observed in statin trials, despite reduced CV events, can be explained by the reduction of coronary inflammation induced by statin which results in more stable macrocalcification.

Aims: To investigate and compare changes in the rates of ischaemic heart disease (IHD) incidence and mortality between 1990 and 2019 in 20 high-income Western European countries with similar public health systems and low cardiovascular risk.Methods and results: The 2020 updated version of the Global Burden of Disease database was searched. Variability and differences in IHD incidence and mortality rates (per 100 000) between countries over time, were calculated. A piecewise linear (join point) regression model was used to identify the slopes of these trends and the points in time at which significant changes in the trends occur. Ischaemic heart disease incidence and mortality rates varied widely between countries but decreased for all between 1990 and 2019. The relative change was greater for mortality than for incidence. Ischaemic heart disease incidence rates declined by approximately 36% between 1990 and 2019, while mortality declined by approximately 60%. Breakpoint analysis showed that the largest decreases in incidence and mortality occurred between 1990 and 2009 (−32%, −52%, respectively), with a much slower decrease after that (−5.9%, −17.6%, respectively), and even a slight increase for some countries in recent years. The decline in both incidence and mortality was lower in the Mediterranean European countries compared to the Nordic and Central European regions.Conclusions: In the Western European countries studied, the decline in age-standardized IHD incidence over three decades was slower than the decline in age-standardized IHD mortality. Decreasing trends of both IHD incidence and mortality has substantially slowed, and for some countries flattened, in more recent years.

Identifying patients at increased risk of coronary artery disease, before the atherosclerotic complications become clinically evident, is the aim of cardiovascular prevention. Imaging techniques provide direct assessment of coronary atherosclerotic burden and pathological characteristics of atherosclerotic lesions which may predict the progression of disease. Atherosclerosis imaging has been traditionally based on the evaluation of coronary luminal narrowing and stenosis. However, the degree of arterial obstruction is a poor predictor of subsequent acute events. More recent techniques focus on the high-resolution visualization of the arterial wall and the coronary plaques. Most acute coronary events are triggered by plaque rupture or erosion. Hence, atherosclerotic plaque imaging has generally focused on the detection of vulnerable plaque prone to rupture. However, atherosclerosis is a dynamic process and the plaque morphology and composition may change over time. Most vulnerable plaques undergo progressive transformation from high-risk to more stable and heavily calcified lesions, while others undergo subclinical rupture and healing. Although extensive plaque calcification is often associated with stable atherosclerosis, the extent of coronary artery calcification strongly correlates with the degree of atherosclerosis and with the rate of future cardiac events. Inflammation has a central role in atherogenesis, from plaque formation to rupture, hence in the development of acute coronary events. Morphologic plaque assessment, both invasive and non-invasive, gives limited information as to the current activity of the atherosclerotic disease. The addition of nuclear imaging, based on radioactive tracers targeted to the inflammatory components of the plaques, provides a highly sensitive assessment of coronary disease activity, thus distinguishing those patients who have stable disease from those with active plaque inflammation.