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Coronary artery disease (CAD) is the leading cause of mortality globally. Although substantial advances have been made in the diagnosis, management, and risk stratification of CAD, there is still a need for novel diagnostic biomarkers and new therapeutic targets to prevent the epidemic of the disease. Recently, growing evidence has linked dysregulated microRNAs (miRNAs) to cardiovascular diseases, including CAD. miRNAs are endogenous, stable, single-stranded, short, non-coding RNAs, and may have utility as diagnostic and prognostic biomarkers for CAD. Dysregulated miRNAs are involved in regulating lipid and glucose homeostasis pathways, reninangiotensin- aldosterone pathways, inflammation, endothelial and vascular smooth cell phenotypes promoting atherosclerotic plaque development, progression, and instability. Additionally, miRNAs are stable and easily accessible in the extracellular space, may reside in microvesicles, and are detectable in serum or plasma, making them attractive biomarkers for the diagnosis and prognosis of cardiovascular disease. Accumulating studies suggest that miRNAs could be useful biomarkers for early discrimination of patients presenting with myocarditis or Takotsubo syndrome from those with a diagnosis of acute myocardial infarction, early prognostication of patients presenting with acute coronary syndromes, and accurate detection of left ventricular remodeling after a chronic or acute ischemic event. Moreover, miRNAs represent potential novel therapeutic targets for CAD or other cardiovascular diseases. This review provides an overview of the effects of the entire spectrum of CAD, its major risk factors, and complications on levels of circulating miRNAs, as well as the limitations and challenges of their potential clinical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background It is still unknown whether traditional risk factors may have a sex-specific impact on coronary artery disease (CAD) burden. Methods and Results We identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries; Clini​calTr​ials.gov, NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between traditional risk factors and severity of CAD and its relationship with 30-day mortality. Relative risk (RR) ratios and 95% CIs were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Estimates were compared by test of interaction on the log scale. Severity of CAD was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD. The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49 (95% CI, 0.41-0.60) and among those with diabetes mellitus was 0.89 (95% CI, 0.62-1.29), with an interaction by diabetes mellitus status of P =0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41-0.61) in nonsmokers to 0.75 (95% CI, 0.54-1.03) in current smokers, with an interaction by smoking status of P =0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR, 1.75; 95% CI, 1.48-2.07). No sex differences in mortality were observed in patients with nonobstructive CAD. Conclusions Obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01218776.

Prevalence of peripheral arterial disease in patients with coronary artery disease is considerably higher than in the general population. A graded increase in the risk of major cardiovascular events in a variety of clinical settings is associated with the number of arterial beds affected by peripheral arterial disease. This is not surprising, considering that both coronary artery disease and peripheral arterial disease are linked to a higher prevalence of cardiovascular risk factors and a greater incidence of atherosclerotic burden. Aggressive lipid lowering therapy is associated with less coronary and peripheral arterial disease progression and greater regression. On the contrary, blood pressure therapy should be carefully managed, considering the association of both high and low values of pressure with adverse outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A growing amount of data is increasingly showing the relevance of coronary microvascular dysfunction (CMVD) in several clinical contexts. This article reviews techniques and clinical investigations of the main noninvasive and invasive methods proposed to study coronary microcirculation and to identify CMVD in the presence of normal coronary arteries, also trying to provide indications for their application in clinical practice.

Background: Vagal fibres are distributed both in the perivascular connective tissue and in the adventitia around the circumference of arteries, and contribute to coronary artery dilation. The aim of the manuscript is to examine whether morphologic changes of the vessel wall due to the atherosclerotic process might be associated with autonomic nervous system dysfunction., Methods and Results: We studied 42 patients with single vessel disease referred for percutaneous coronary revascularization. Patients underwent intravascular ultrasound at the site of the ischemia-related artery before intervention. The autonomic nervous system activity was assessed by the analysis of heart rate variability (HRV) in the frequency domain. The high frequencies (HF) are predominantly under the influence of the parasympathetic system, while the low/high frequency (LF/HF) ratio represents an index of sympatho-vagal balance. Plaque plus media cross-sectional area was inversely related to HF components (r=-0.34, p<0.05), and directly related to LF/HF ratio (r=0.38, p<0.05). Patients with expansive remodeling showed lower HF values (0.07+/-0.06 nu versus 0.14+/-0.09 nu, p<0.01) and higher LH/HF ratio (2.1+/-1.1 versus 1.4+/-1.1; p<0.05). LF changes were independent of any morphologic features. On multivariate analyses the remodeling index was the only independent determinant of HF and LF/HF ratio., Conclusions: Outward stretch of the vessel wall behind the plaque, as a consequence of increasing plaque size and expansive arterial remodeling is associated to autonomic dysfunction namely due to impairment of the vagal tone. It is unknown if remodeling is a cause of vagal impairment or if vagal impairment may contribute to arterial remodeling.

Optical coherence tomography (OCT) is a recently developed technology capable of micron-scale imaging. Its high resolution (10-20 microm) makes intravascular OCT imaging the most interesting method for assessing atherosclerotic plaque microstructure in patients suffering from coronary artery disease. OCT allowed measurement of the thickness of the plaque fibrous cap, as well as identification of intima, media, and external elastic membrane in patients with normal coronary arteries. However, significant limitations still exist, including poor penetration in non-transparent tissue. The aim of this review is to give an update on OCT on the basis of the existing literature, with an overview of the strong and weak features of this technique.

Mechanisms underlying coronary spasm are still poorly understood. The aim of the study was to assess the hypothesis that fluctuations in the development of coronary spasm might reflect inputs from the adjacent esophageal system. We enrolled patients admitted to the coronary care unit for episodes of nocturnal angina. Seven patients with variant angina and five with coronary artery disease (CAD) had concurrent ECG and esophageal manometric monitoring. ECG monitoring documented 28 episodes of ST elevation in variant angina patients and 16 episodes of ST depression in CAD patients. Manometric analysis showed that esophageal spasms resulted remarkably more frequently in variant angina patients (143 total spasms; individual range 9-31) than in CAD patients (20 total spasms; individual range 0-9; P < 0.01). Time series analysis was used to assess fluctuations in the occurrence of abnormal esophageal waves and its relationship with spontaneous episodes of ST shift. Episodes of esophageal spasm in CAD were sporadic (<1 in 30 min) and not related to ECG-recorded ischemia. In the variant angina group, esophageal spasms were time related to ischemia (>1 into 5 min before ECG-recorded ischemia) (P < 0.05). A bidirectional analysis of causal effects showed that the influence processes between esophageal and coronary spasms were mutual and reciprocal (transfer function model, P < 0.05) in variant angina. We concluded that in variant angina patients, episodes of esophageal spasms and myocardial ischemia influenced each other. Mechanisms that cause esophageal spasm can feed back to produce coronary spasm. Coronary spasm may feed forward to produce additional episodes of esophageal spasm.

The term "chest pain with normal coronary arteries" encompasses a large number of different cardiac pathophysiological abnormalities, including impairment of coronary flow reserve, endothelial dysfunction, and early atherosclerosis that, in most cases, cannot be readily differentiated one from the other. To study early coronary atherosclerosis, physicians must look beyond contrast filled arteries (so called lumenology). Angiograms cannot evaluate the vessel wall, plaque distribution and composition or other morphology. Plaques are often angiographically not visible due to their small size and compensatory enlargement (outward remodeling) of the coronary arteries. As a result, the search for an underlying atherosclerotic process remains ongoing. Available clinical studies showed that many patients with chest pain and normal angiography have early atherosclerosis as documented by intravascular ultrasound imaging, reduced coronary flow reserve and coronary endothelial dysfunction. Additional studies showed that patients presenting with normal coronary angiography have recurrent coronary events at long-term follow up. Research to determine if improved diagnosis and treatment of quantitatively low degrees of atherosclerosis lead to improved outcomes of patients with normal angiography should be undertaken.

Aims: Cardio-cardiac reflexes may be evoked by both myocardial ischaemia and coronary occlusion itself. The aim of the study was to assess the intrapatient behaviour of autonomic nervous system balance during spontaneous and balloon-induced coronary ischaemia., Methods and Results: We studied a group of patients admitted to the coronary care unit for acute coronary syndrome without ST-segment elevation who experienced spontaneous episodes of myocardial ischaemia during bed rest and ECG monitoring. The inclusion criterion was 80-90% lumen stenosis, amenable to angioplasty. Balloon coronary occlusion was performed at 4-6 atmospheres for 120 s. Autonomic nervous system activity was assessed by heart rate variability (HRV) analysis in frequency domain. We analysed 14 episodes of spontaneous ischaemia and 14 episodes of balloon coronary occlusion. During spontaneous ischaemia, HRV showed an increase in the low/high frequencies ratio (11.8 +/- 5.7), as compared to 5 min before and 5 min after (4.4 +/- 2.7 and 3.9 +/- 1.8, respectively) (p = 0.001). The opposite occurred during balloon coronary occlusion (0.8 +/- 0.4 vs. 3.9 +/- 2.0 and 5.1 +/- 2.1, respectively; p = 0.001)., Conclusions: Balloon inflation and occlusion evokes baroreceptor vagal predominance in response to a stretch stimulus of the coronary artery. Conversely, spontaneous occlusion during unstable angina is accompanied by naturally occurring sympathetic activation. Sympathetic activation may have a role in the natural history of the disease., (Copyright 2004 Elsevier Ltd)